cell
Homozygous HLA stem cells address the rejection issue in cell transplants by matching the donor and recipient's immune profiles, thereby improving transplant compatibility and success.
Patent Information
- Application Number
- JP2024096465
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-06-14
- Publication Date
- 2025-12-25
AI Technical Summary
Existing cell transplants face significant rejection issues due to differences in human leukocyte antigen (HLA) combinations between donor and recipient, leading to immune system recognition of allogeneic cells as foreign bodies.
Development of stem cells, particularly pluripotent stem cells, that are homozygous for specific HLA alleles such as HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1, and HLA-DRB3, to minimize immune rejection.
The use of homozygous HLA stem cells reduces the likelihood of rejection by aligning the donor cells' HLA profile with the recipient, enhancing the compatibility and success of cell transplants.
Smart Images

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Abstract
Description
[Technical Field]
[0001] The present invention relates to a cell. [Background technology]
[0002] Major histocompatibility complexes (MHCs), known as human leukocyte antigens (HLAs) in humans, are expressed in most cells and tissues. HLAs have six main antigen loci: A, B, C, DR, DQ, and DP. Furthermore, each is composed of complex combinations of dozens of different types (alleles). Therefore, there are tens of thousands of possible combinations. HLAs play an important role in the immune system within the human body, and their primary role is antigen presentation for self- and other-recognition. When cells or tissues from a non-patient are transplanted into a patient, the HLAs on the allogeneic cells are recognized as foreign bodies by immune cells such as T cells, potentially resulting in rejection (see, for example, Patent Documents 1 to 5). [Prior art documents] [Patent documents]
[0003] [Patent Document 1] Patent No. 6815453 [Patent Document 2] Patent No. 6933898 [Patent Document 3] Patent No. 7212615 [Patent Document 4] Patent No. 7385281 [Patent Document 5] Patent No. 7440027 Summary of the Invention [Problem to be solved by the invention]
[0004] One of the objects of the present invention is to provide cells that cause minimal rejection when transplanted. [Means for solving the problem]
[0005] According to an aspect of the present invention, there is provided a cell that is homozygous for at least one, two, three, four, or all of the group consisting of HLA-A*01:01g, HLA-B*08:01g, HLA-DRB1*03:01, HLA-C*07:01g, HLA-DQB1*02:01g, and HLA-DRB3*01:01.
[0006] The cells may be stem cells.
[0007] The cells may be pluripotent stem cells.
[0008] According to an embodiment of the present invention, HLA-A * Cells homozygous for 01:01g are provided.
[0009] The above cells are HLA-B * They may be homozygous for 08:01g.
[0010] The above cells are HLA-DRB1 * The patient may be homozygous for 03:01.
[0011] The above cells are HLA-C * 07:01g may be homozygous.
[0012] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0013] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0014] The cells may be stem cells.
[0015] The cells may be pluripotent stem cells.
[0016] According to an embodiment of the present invention, HLA-B *Cells homozygous for 08:01g are provided.
[0017] The above cells are HLA-DRB1 * The patient may be homozygous for 03:01.
[0018] The above cells are HLA-C * 07:01g may be homozygous.
[0019] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0020] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0021] The cells may be stem cells.
[0022] The cells may be pluripotent stem cells.
[0023] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 03:01 are provided.
[0024] The above cells are HLA-C * 07:01g may be homozygous.
[0025] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0026] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0027] The cells may be stem cells.
[0028] The cells may be pluripotent stem cells.
[0029] According to an embodiment of the present invention, HLA-C * Cells homozygous for 07:01g are provided.
[0030] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0031] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0032] The cells may be stem cells.
[0033] The cells may be pluripotent stem cells.
[0034] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 02:01g are provided.
[0035] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0036] The cells may be stem cells.
[0037] The cells may be pluripotent stem cells.
[0038] According to an embodiment of the present invention, HLA-DRB3 * Cells homozygous for 01:01 are provided.
[0039] The cells may be stem cells.
[0040] The cells may be pluripotent stem cells.
[0041] According to an embodiment of the present invention, HLA-A * 03:01g, HLA-B * 07:02g, HLA-DRB1 * 15:01, HLA-C *07:02g, HLA-DQB1 * 06:02, and HLA-DRB5 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01.
[0042] The cells may be stem cells.
[0043] The cells may be pluripotent stem cells.
[0044] According to an embodiment of the present invention, HLA-A * Cells homozygous for 03:01g are provided.
[0045] The above cells are HLA-B * They may be homozygous for 07:02g.
[0046] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0047] The above cells are HLA-C * They may be homozygous for 07:02g.
[0048] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0049] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0050] The cells may be stem cells.
[0051] The cells may be pluripotent stem cells.
[0052] According to an embodiment of the present invention, HLA-B * Cells homozygously carrying 07:02g are provided.
[0053] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0054] The above cells are HLA-C * They may be homozygous for 07:02g.
[0055] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0056] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0057] The cells may be stem cells.
[0058] The cells may be pluripotent stem cells.
[0059] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 15:01 are provided.
[0060] The above cells are HLA-C * They may be homozygous for 07:02g.
[0061] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0062] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0063] The cells may be stem cells.
[0064] The cells may be pluripotent stem cells.
[0065] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 07:02g are provided.
[0066] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0067] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0068] The cells may be stem cells.
[0069] The cells may be pluripotent stem cells.
[0070] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:02 are provided.
[0071] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0072] The cells may be stem cells.
[0073] The cells may be pluripotent stem cells.
[0074] According to an embodiment of the present invention, HLA-DRB5 * Cells homozygous for 01:01 are provided.
[0075] The cells may be stem cells.
[0076] The cells may be pluripotent stem cells.
[0077] According to an aspect of the present invention, there is provided a cell that is homozygous for at least one, two, three, four, or all of the group consisting of HLA-A*02:01g, HLA-B*07:02g, HLA-DRB1*15:01, HLA-C*07:02g, HLA-DQB1*06:02, and HLA-DRB5*01:01.
[0078] The cells may be stem cells.
[0079] The cells may be pluripotent stem cells.
[0080] According to an embodiment of the present invention, HLA-A * Cells homozygous for 02:01g are provided.
[0081] The above cells are HLA-B * They may be homozygous for 07:02g.
[0082] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0083] The above cells are HLA-C * They may be homozygous for 07:02g.
[0084] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0085] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0086] The cells may be stem cells.
[0087] The cells may be pluripotent stem cells.
[0088] According to an embodiment of the present invention, HLA-B * Cells homozygously carrying 07:02g are provided.
[0089] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0090] The above cells are HLA-C * They may be homozygous for 07:02g.
[0091] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0092] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0093] The cells may be stem cells.
[0094] The cells may be pluripotent stem cells.
[0095] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 15:01 are provided.
[0096] The above cells are HLA-C * They may be homozygous for 07:02g.
[0097] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0098] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0099] The cells may be stem cells.
[0100] The cells may be pluripotent stem cells.
[0101] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 07:02g are provided.
[0102] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0103] The above cells express HLA-DRB5* The patient may have 01:01 homozygously.
[0104] The cells may be stem cells.
[0105] The cells may be pluripotent stem cells.
[0106] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:02 are provided.
[0107] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0108] The cells may be stem cells.
[0109] The cells may be pluripotent stem cells.
[0110] According to an embodiment of the present invention, HLA-DRB5 * Cells homozygous for 01:01 are provided.
[0111] The cells may be stem cells.
[0112] The cells may be pluripotent stem cells.
[0113] According to an embodiment of the present invention, HLA-A * 02:01g, HLA-B * 44:02g, HLA-DRB1 * 04:01, HLA-C * 05:01g, HLA-DQB1 * 03:01g, and HLA-DRB4 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01g.
[0114] The cells may be stem cells.
[0115] The cells may be pluripotent stem cells.
[0116] According to an embodiment of the present invention, HLA-A * Cells homozygous for 02:01g are provided.
[0117] The above cells are HLA-B * They may be homozygous for 44:02g.
[0118] The above cells are HLA-DRB1 * The patient may be homozygous for 04:01.
[0119] The above cells are HLA-C * 05:01g may be homozygous.
[0120] The above cells are HLA-DQB1 * 03:01g may be homozygous.
[0121] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0122] The cells may be stem cells.
[0123] The cells may be pluripotent stem cells.
[0124] According to an embodiment of the present invention, HLA-B * Cells homozygous for 44:02g are provided.
[0125] The above cells are HLA-DRB1 * The patient may be homozygous for 04:01.
[0126] The above cells are HLA-C * 05:01g may be homozygous.
[0127] The above cells are HLA-DQB1* 03:01g may be homozygous.
[0128] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0129] The cells may be stem cells.
[0130] The cells may be pluripotent stem cells.
[0131] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 04:01 are provided.
[0132] The above cells are HLA-C * 05:01g may be homozygous.
[0133] The above cells are HLA-DQB1 * 03:01g may be homozygous.
[0134] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0135] The cells may be stem cells.
[0136] The cells may be pluripotent stem cells.
[0137] According to an embodiment of the present invention, HLA-C * Cells homozygous for 05:01g are provided.
[0138] The above cells are HLA-DQB1 * 03:01g may be homozygous.
[0139] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0140] The cells may be stem cells.
[0141] The cells may be pluripotent stem cells.
[0142] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 03:01g are provided.
[0143] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0144] The cells may be stem cells.
[0145] The cells may be pluripotent stem cells.
[0146] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0147] The cells may be stem cells.
[0148] The cells may be pluripotent stem cells.
[0149] According to an embodiment of the present invention, HLA-A * 29:02g, HLA-B * 44:03, HLA-DRB1 * 07:01, HLA-C * 16:01, HLA-DQB1 * 02:01g, and HLA-DRB4 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01g.
[0150] The cells may be stem cells.
[0151] The cells may be pluripotent stem cells.
[0152] According to an embodiment of the present invention, HLA-A * Cells homozygous for 29:02g are provided.
[0153] The above cells are HLA-B * The patient may be homozygous for 44:03.
[0154] The above cells are HLA-DRB1 * The patient may be homozygous for 07:01.
[0155] The above cells are HLA-C * The patient may be homozygous for 16:01.
[0156] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0157] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0158] The cells may be stem cells.
[0159] The cells may be pluripotent stem cells.
[0160] According to an embodiment of the present invention, HLA-B * Cells homozygous for 44:03 are provided.
[0161] The above cells are HLA-DRB1 * The patient may be homozygous for 07:01.
[0162] The above cells are HLA-C * The patient may be homozygous for 16:01.
[0163] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0164] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0165] The cells may be stem cells.
[0166] The cells may be pluripotent stem cells.
[0167] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 07:01 are provided.
[0168] The above cells are HLA-C * The patient may be homozygous for 16:01.
[0169] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0170] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0171] The cells may be stem cells.
[0172] The cells may be pluripotent stem cells.
[0173] According to an embodiment of the present invention, HLA-C * Cells homozygous for 16:01 are provided.
[0174] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0175] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0176] The cells may be stem cells.
[0177] The cells may be pluripotent stem cells.
[0178] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 02:01g are provided.
[0179] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0180] The cells may be stem cells.
[0181] The cells may be pluripotent stem cells.
[0182] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0183] The cells may be stem cells.
[0184] The cells may be pluripotent stem cells.
[0185] According to an embodiment of the present invention, HLA-A * 03:01g, HLA-B * 35:01g, HLA-C * 04:01g, HLA-DRB1 * 01:01, HLA-DQB1 * 05:01, and HLA-DRBX * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of NNNN.
[0186] The cells may be stem cells.
[0187] The cells may be pluripotent stem cells.
[0188] According to an embodiment of the present invention, HLA-A * Cells homozygous for 03:01g are provided.
[0189] The above cells are HLA-B * 35:01g may be homozygous.
[0190] The above cells are HLA-C * 04:01g may be homozygous.
[0191] The above cells are HLA-DRB1 * The patient may have 01:01 homozygously.
[0192] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0193] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0194] The cells may be stem cells.
[0195] The cells may be pluripotent stem cells.
[0196] According to an embodiment of the present invention, HLA-B * Cells homozygous for 35:01g are provided.
[0197] The above cells are HLA-C * 04:01g may be homozygous.
[0198] The above cells are HLA-DRB1 * The patient may have 01:01 homozygously.
[0199] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0200] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0201] The cells may be stem cells.
[0202] The cells may be pluripotent stem cells.
[0203] According to an embodiment of the present invention, HLA-C * Cells homozygous for 04:01g are provided.
[0204] The above cells are HLA-DRB1 * The patient may have 01:01 homozygously.
[0205] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0206] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0207] The cells may be stem cells.
[0208] The cells may be pluripotent stem cells.
[0209] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 01:01 are provided.
[0210] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0211] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0212] The cells may be stem cells.
[0213] The cells may be pluripotent stem cells.
[0214] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 05:01 are provided.
[0215] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0216] The cells may be stem cells.
[0217] The cells may be pluripotent stem cells.
[0218] According to an embodiment of the present invention, HLA-DRBX * Cells homozygously carrying NNNN are provided.
[0219] The cells may be stem cells.
[0220] The cells may be pluripotent stem cells.
[0221] According to an embodiment of the present invention, HLA-A * 02:01g, HLA-B * 08:01g, HLA-C * 07:01g, HLA-DRB1 * 03:01, HLA-DQB1 * 02:01g, and HLA-DRB3 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01.
[0222] The cells may be stem cells.
[0223] The cells may be pluripotent stem cells.
[0224] According to an embodiment of the present invention, HLA-A * Cells homozygous for 02:01g are provided.
[0225] The above cells are HLA-B *They may be homozygous for 08:01g.
[0226] The above cells are HLA-C * 07:01g may be homozygous.
[0227] The above cells are HLA-DRB1 * The patient may be homozygous for 03:01.
[0228] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0229] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0230] The cells may be stem cells.
[0231] The cells may be pluripotent stem cells.
[0232] According to an embodiment of the present invention, HLA-B * Cells homozygous for 08:01g are provided.
[0233] The above cells are HLA-C * 07:01g may be homozygous.
[0234] The above cells are HLA-DRB1 * The patient may be homozygous for 03:01.
[0235] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0236] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0237] The cells may be stem cells.
[0238] The cells may be pluripotent stem cells.
[0239] According to an embodiment of the present invention, HLA-C * Cells homozygous for 07:01g are provided.
[0240] The above cells are HLA-DRB1 * The patient may be homozygous for 03:01.
[0241] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0242] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0243] The cells may be stem cells.
[0244] The cells may be pluripotent stem cells.
[0245] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 03:01 are provided.
[0246] The above cells are HLA-DQB1 * 02:01g may be homozygous.
[0247] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0248] The cells may be stem cells.
[0249] The cells may be pluripotent stem cells.
[0250] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 02:01g are provided.
[0251] The above cells express HLA-DRB3 * The patient may have 01:01 homozygously.
[0252] The cells may be stem cells.
[0253] The cells may be pluripotent stem cells.
[0254] According to an embodiment of the present invention, HLA-DRB3 * Cells homozygous for 01:01 are provided.
[0255] The cells may be stem cells.
[0256] The cells may be pluripotent stem cells.
[0257] According to an embodiment of the present invention, HLA-A * 01:01g, HLA-B * 57:01g, HLA-C * 06:02g, HLA-DRB1 * 07:01, HLA-DQB1 * 03:03g, and HLA-DRB4 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01g.
[0258] The cells may be stem cells.
[0259] The cells may be pluripotent stem cells.
[0260] According to an embodiment of the present invention, HLA-A * Cells homozygous for 01:01g are provided.
[0261] The above cells are HLA-B * 57:01g may be homozygous.
[0262] The above cells are HLA-C * They may be homozygous for 06:02g.
[0263] The above cells are HLA-DRB1 * The patient may be homozygous for 07:01.
[0264] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0265] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0266] The cells may be stem cells.
[0267] The cells may be pluripotent stem cells.
[0268] According to an embodiment of the present invention, HLA-B * Cells homozygous for 57:01g are provided.
[0269] The above cells are HLA-C * They may be homozygous for 06:02g.
[0270] The above cells are HLA-DRB1 * The patient may be homozygous for 07:01.
[0271] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0272] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0273] The cells may be stem cells.
[0274] The cells may be pluripotent stem cells.
[0275] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 06:02g are provided.
[0276] The above cells are HLA-DRB1 * The patient may be homozygous for 07:01.
[0277] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0278] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0279] The cells may be stem cells.
[0280] The cells may be pluripotent stem cells.
[0281] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 07:01 are provided.
[0282] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0283] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0284] The cells may be stem cells.
[0285] The cells may be pluripotent stem cells.
[0286] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 03:03g are provided.
[0287] The above cells are HLA-DRB4* The patient may be homozygous for 01:01g.
[0288] The cells may be stem cells.
[0289] The cells may be pluripotent stem cells.
[0290] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0291] The cells may be stem cells.
[0292] The cells may be pluripotent stem cells.
[0293] According to an embodiment of the present invention, HLA-A * 02:01g, HLA-B * 40:01g, HLA-C * 03:04g, HLA-DRB1 * 13:02, HLA-DQB1 * 06:04g, and HLA-DRB3 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of: 03:01.
[0294] The cells may be stem cells.
[0295] The cells may be pluripotent stem cells.
[0296] According to an embodiment of the present invention, HLA-A * Cells homozygous for 02:01g are provided.
[0297] The above cells are HLA-B * They may be homozygous for 40:01g.
[0298] The above cells are HLA-C * 03:04g may be homozygous.
[0299] The above cells are HLA-DRB1 * The patient may be homozygous for 13:02.
[0300] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0301] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0302] The cells may be stem cells.
[0303] The cells may be pluripotent stem cells.
[0304] According to an embodiment of the present invention, HLA-B * Cells homozygous for 40:01g are provided.
[0305] The above cells are HLA-C * 03:04g may be homozygous.
[0306] The above cells are HLA-DRB1 * The patient may be homozygous for 13:02.
[0307] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0308] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0309] The cells may be stem cells.
[0310] The cells may be pluripotent stem cells.
[0311] According to an embodiment of the present invention, HLA-C *Cells homozygously carrying 03:04g are provided.
[0312] The above cells are HLA-DRB1 * The patient may be homozygous for 13:02.
[0313] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0314] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0315] The cells may be stem cells.
[0316] The cells may be pluripotent stem cells.
[0317] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 13:02 are provided.
[0318] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0319] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0320] The cells may be stem cells.
[0321] The cells may be pluripotent stem cells.
[0322] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:04g are provided.
[0323] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0324] The cells may be stem cells.
[0325] The cells may be pluripotent stem cells.
[0326] According to an embodiment of the present invention, HLA-DRB3 * Cells homozygous for 03:01 are provided.
[0327] The cells may be stem cells.
[0328] The cells may be pluripotent stem cells.
[0329] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-B * 07:02g, HLA-C * 07:02g, HLA-DRB1 * 15:01, HLA-DQB1 * 06:02, and HLA-DRB5 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 01:01.
[0330] The cells may be stem cells.
[0331] The cells may be pluripotent stem cells.
[0332] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0333] The above cells are HLA-B * They may be homozygous for 07:02g.
[0334] The above cells are HLA-C * They may be homozygous for 07:02g.
[0335] The above cells are HLA-DRB1 *The patient may be homozygous for 15:01.
[0336] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0337] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0338] The cells may be stem cells.
[0339] The cells may be pluripotent stem cells.
[0340] According to an embodiment of the present invention, HLA-B * Cells homozygously carrying 07:02g are provided.
[0341] The above cells are HLA-C * They may be homozygous for 07:02g.
[0342] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0343] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0344] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0345] The cells may be stem cells.
[0346] The cells may be pluripotent stem cells.
[0347] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 07:02g are provided.
[0348] The above cells are HLA-DRB1 * The patient may be homozygous for 15:01.
[0349] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0350] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0351] The cells may be stem cells.
[0352] The cells may be pluripotent stem cells.
[0353] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 15:01 are provided.
[0354] The above cells are HLA-DQB1 * The patient may be homozygous for 06:02.
[0355] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0356] The cells may be stem cells.
[0357] The cells may be pluripotent stem cells.
[0358] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:02 are provided.
[0359] The above cells express HLA-DRB5 * The patient may have 01:01 homozygously.
[0360] The cells may be stem cells.
[0361] The cells may be pluripotent stem cells.
[0362] According to an embodiment of the present invention, HLA-DRB5 * Cells homozygous for 01:01 are provided.
[0363] The cells may be stem cells.
[0364] The cells may be pluripotent stem cells.
[0365] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-B * 52:01g, HLA-DRB1 * 15:02, HLA-C * 12:02, HLA-DRB5 * 01:02g, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of: 06:01.
[0366] The cells may be stem cells.
[0367] The cells may be pluripotent stem cells.
[0368] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0369] The above cells are HLA-B * 52:01g may be homozygous.
[0370] The above cells are HLA-DRB1 * The patient may be homozygous for 15:02.
[0371] The above cells are HLA-C * The patient may be homozygous for 12:02.
[0372] The above cells express HLA-DRB5 * They may be homozygous for 01:02g.
[0373] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0374] The cells may be stem cells.
[0375] The cells may be pluripotent stem cells.
[0376] According to an embodiment of the present invention, HLA-B * Cells homozygous for 52:01g are provided.
[0377] The above cells are HLA-DRB1 * The patient may be homozygous for 15:02.
[0378] The above cells are HLA-C * The patient may be homozygous for 12:02.
[0379] The above cells express HLA-DRB5 * They may be homozygous for 01:02g.
[0380] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0381] The cells may be stem cells.
[0382] The cells may be pluripotent stem cells.
[0383] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 15:02 are provided.
[0384] The above cells are HLA-C * The patient may be homozygous for 12:02.
[0385] The above cells express HLA-DRB5 * They may be homozygous for 01:02g.
[0386] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0387] The cells may be stem cells.
[0388] The cells may be pluripotent stem cells.
[0389] According to an embodiment of the present invention, HLA-C * Cells homozygous for 12:02 are provided.
[0390] The above cells express HLA-DRB5 * They may be homozygous for 01:02g.
[0391] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0392] The cells may be stem cells.
[0393] The cells may be pluripotent stem cells.
[0394] According to an embodiment of the present invention, HLA-DRB5 * Cells homozygously carrying 01:02g are provided.
[0395] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0396] The cells may be stem cells.
[0397] The cells may be pluripotent stem cells.
[0398] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:01 are provided.
[0399] The cells may be stem cells.
[0400] The cells may be pluripotent stem cells.
[0401] According to an embodiment of the present invention, HLA-A * 33:03g, HLA-B * 44:03, HLA-DRB1 * 13:02, HLA-C * 14:03, HLA-DRB3 * 03:01, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 06:04g.
[0402] The cells may be stem cells.
[0403] The cells may be pluripotent stem cells.
[0404] According to an embodiment of the present invention, HLA-A * Cells homozygous for 33:03g are provided.
[0405] The above cells are HLA-B * The patient may be homozygous for 44:03.
[0406] The above cells are HLA-DRB1 * The patient may be homozygous for 13:02.
[0407] The above cells are HLA-C * The patient may be homozygous for 14:03.
[0408] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0409] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0410] The cells may be stem cells.
[0411] The cells may be pluripotent stem cells.
[0412] According to an embodiment of the present invention, HLA-B * Cells homozygous for 44:03 are provided.
[0413] The above cells are HLA-DRB1 * The patient may be homozygous for 13:02.
[0414] The above cells are HLA-C * The patient may be homozygous for 14:03.
[0415] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0416] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0417] The cells may be stem cells.
[0418] The cells may be pluripotent stem cells.
[0419] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 13:02 are provided.
[0420] The above cells are HLA-C * The patient may be homozygous for 14:03.
[0421] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0422] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0423] The cells may be stem cells.
[0424] The cells may be pluripotent stem cells.
[0425] According to an embodiment of the present invention, HLA-C * Cells homozygous for 14:03 are provided.
[0426] The above cells express HLA-DRB3 * The patient may be homozygous for 03:01.
[0427] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0428] The cells may be stem cells.
[0429] The cells may be pluripotent stem cells.
[0430] According to an embodiment of the present invention, HLA-DRB3 * Cells homozygous for 03:01 are provided.
[0431] The above cells are HLA-DQB1 * They may be homozygous for 06:04g.
[0432] The cells may be stem cells.
[0433] The cells may be pluripotent stem cells.
[0434] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:04g are provided.
[0435] The cells may be stem cells.
[0436] The cells may be pluripotent stem cells.
[0437] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-B * 07:02g, HLA-DRB1 * 01:01, HLA-C * 07:02g, HLA-DRBX * NNNN and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of: 05:01.
[0438] The cells may be stem cells.
[0439] The cells may be pluripotent stem cells.
[0440] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0441] The above cells are HLA-B * They may be homozygous for 07:02g.
[0442] The above cells are HLA-DRB1 * The patient may have 01:01 homozygously.
[0443] The above cells are HLA-C * They may be homozygous for 07:02g.
[0444] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0445] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0446] The cells may be stem cells.
[0447] The cells may be pluripotent stem cells.
[0448] According to an embodiment of the present invention, HLA-B * Cells homozygously carrying 07:02g are provided.
[0449] The above cells are HLA-DRB1 * The patient may have 01:01 homozygously.
[0450] The above cells are HLA-C * They may be homozygous for 07:02g.
[0451] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0452] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0453] The cells may be stem cells.
[0454] The cells may be pluripotent stem cells.
[0455] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 01:01 are provided.
[0456] The above cells are HLA-C * They may be homozygous for 07:02g.
[0457] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0458] The above cells are HLA-DQB1 *The patient may be homozygous for 05:01.
[0459] The cells may be stem cells.
[0460] The cells may be pluripotent stem cells.
[0461] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 07:02g are provided.
[0462] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0463] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0464] The cells may be stem cells.
[0465] The cells may be pluripotent stem cells.
[0466] According to an embodiment of the present invention, HLA-DRBX * Cells homozygously carrying NNNN are provided.
[0467] The above cells are HLA-DQB1 * The patient may be homozygous for 05:01.
[0468] The cells may be stem cells.
[0469] The cells may be pluripotent stem cells.
[0470] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 05:01 are provided.
[0471] The cells may be stem cells.
[0472] The cells may be pluripotent stem cells.
[0473] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-B * 54:01g, HLA-DRB1 * 04:05, HLA-C * 01:02g, HLA-DRB4 * 01:01g, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 04:01g.
[0474] The cells may be stem cells.
[0475] The cells may be pluripotent stem cells.
[0476] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0477] The above cells are HLA-B * 54:01g may be homozygous.
[0478] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0479] The above cells are HLA-C * They may be homozygous for 01:02g.
[0480] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0481] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0482] The cells may be stem cells.
[0483] The cells may be pluripotent stem cells.
[0484] According to an embodiment of the present invention, HLA-B * Cells homozygous for 54:01g are provided.
[0485] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0486] The above cells are HLA-C * They may be homozygous for 01:02g.
[0487] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0488] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0489] The cells may be stem cells.
[0490] The cells may be pluripotent stem cells.
[0491] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 04:05 are provided.
[0492] The above cells are HLA-C * They may be homozygous for 01:02g.
[0493] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0494] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0495] The cells may be stem cells.
[0496] The cells may be pluripotent stem cells.
[0497] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 01:02g are provided.
[0498] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0499] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0500] The cells may be stem cells.
[0501] The cells may be pluripotent stem cells.
[0502] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0503] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0504] The cells may be stem cells.
[0505] The cells may be pluripotent stem cells.
[0506] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 04:01g are provided.
[0507] The cells may be stem cells.
[0508] The cells may be pluripotent stem cells.
[0509] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-B * 59:01, HLA-DRB1 * 04:05, HLA-C * 01:02g, HLA-DRB4 * 01:01g, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 04:01g.
[0510] The cells may be stem cells.
[0511] The cells may be pluripotent stem cells.
[0512] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0513] The above cells are HLA-B * The patient may be homozygous for 59:01.
[0514] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0515] The above cells are HLA-C * They may be homozygous for 01:02g.
[0516] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0517] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0518] The cells may be stem cells.
[0519] The cells may be pluripotent stem cells.
[0520] According to an embodiment of the present invention, HLA-B * Cells homozygous for 59:01 are provided.
[0521] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0522] The above cells are HLA-C * They may be homozygous for 01:02g.
[0523] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0524] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0525] The cells may be stem cells.
[0526] The cells may be pluripotent stem cells.
[0527] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 04:05 are provided.
[0528] The above cells are HLA-C * They may be homozygous for 01:02g.
[0529] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0530] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0531] The cells may be stem cells.
[0532] The cells may be pluripotent stem cells.
[0533] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 01:02g are provided.
[0534] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0535] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0536] The cells may be stem cells.
[0537] The cells may be pluripotent stem cells.
[0538] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0539] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0540] The cells may be stem cells.
[0541] The cells may be pluripotent stem cells.
[0542] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 04:01g are provided.
[0543] The cells may be stem cells.
[0544] The cells may be pluripotent stem cells.
[0545] According to an embodiment of the present invention, HLA-A * 02:07g, HLA-C* 01:02g, HLA-B * 46:01g, HLA-DRBX * NNNN, HLA-DRB1 * 08:03, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of: 06:01.
[0546] The cells may be stem cells.
[0547] The cells may be pluripotent stem cells.
[0548] According to an embodiment of the present invention, HLA-A * Cells homozygously carrying 02:07g are provided.
[0549] The above cells are HLA-C * They may be homozygous for 01:02g.
[0550] The above cells are HLA-B * 46:01g may be homozygous.
[0551] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0552] The above cells are HLA-DRB1 * The patient may be homozygous for 08:03.
[0553] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0554] The cells may be stem cells.
[0555] The cells may be pluripotent stem cells.
[0556] According to an embodiment of the present invention, HLA-C *Cells homozygously carrying 01:02g are provided.
[0557] The above cells are HLA-B * 46:01g may be homozygous.
[0558] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0559] The above cells are HLA-DRB1 * The patient may be homozygous for 08:03.
[0560] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0561] The cells may be stem cells.
[0562] The cells may be pluripotent stem cells.
[0563] According to an embodiment of the present invention, HLA-B * Cells homozygous for 46:01g are provided.
[0564] The above cells are HLA-DRBX * The patient may have homozygous NNNN.
[0565] The above cells are HLA-DRB1 * The patient may be homozygous for 08:03.
[0566] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0567] The cells may be stem cells.
[0568] The cells may be pluripotent stem cells.
[0569] According to an embodiment of the present invention, HLA-DRBX * Cells homozygously carrying NNNN are provided.
[0570] The above cells are HLA-DRB1 * The patient may be homozygous for 08:03.
[0571] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0572] The cells may be stem cells.
[0573] The cells may be pluripotent stem cells.
[0574] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 08:03 are provided.
[0575] The above cells are HLA-DQB1 * The patient may be homozygous for 06:01.
[0576] The cells may be stem cells.
[0577] The cells may be pluripotent stem cells.
[0578] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 06:01 are provided.
[0579] The cells may be stem cells.
[0580] The cells may be pluripotent stem cells.
[0581] According to an embodiment of the present invention, HLA-A * 11:01g, HLA-C * 04:01g, HLA-B * 15:01g, HLA-DRB4 *01:01g, HLA-DRB1 * 04:06, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 03:02g.
[0582] The cells may be stem cells.
[0583] The cells may be pluripotent stem cells.
[0584] According to an embodiment of the present invention, HLA-A * Cells homozygous for 11:01g are provided.
[0585] The above cells are HLA-C * 04:01g may be homozygous.
[0586] The above cells are HLA-B * They may be homozygous for 15:01g.
[0587] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0588] The above cells are HLA-DRB1 * The patient may be homozygous for 04:06.
[0589] The above cells are HLA-DQB1 * 03:02g may be homozygous.
[0590] The cells may be stem cells.
[0591] The cells may be pluripotent stem cells.
[0592] According to an embodiment of the present invention, HLA-C * Cells homozygous for 04:01g are provided.
[0593] The above cells are HLA-B * They may be homozygous for 15:01g.
[0594] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0595] The above cells are HLA-DRB1 * The patient may be homozygous for 04:06.
[0596] The above cells are HLA-DQB1 * 03:02g may be homozygous.
[0597] The cells may be stem cells.
[0598] The cells may be pluripotent stem cells.
[0599] According to an embodiment of the present invention, HLA-B * Cells homozygous for 15:01g are provided.
[0600] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0601] The above cells are HLA-DRB1 * The patient may be homozygous for 04:06.
[0602] The above cells are HLA-DQB1 * 03:02g may be homozygous.
[0603] The cells may be stem cells.
[0604] The cells may be pluripotent stem cells.
[0605] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0606] The above cells are HLA-DRB1 * The patient may be homozygous for 04:06.
[0607] The above cells are HLA-DQB1 * 03:02g may be homozygous.
[0608] The cells may be stem cells.
[0609] The cells may be pluripotent stem cells.
[0610] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 04:06 are provided.
[0611] The above cells are HLA-DQB1 * 03:02g may be homozygous.
[0612] The cells may be stem cells.
[0613] The cells may be pluripotent stem cells.
[0614] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygously carrying 03:02g are provided.
[0615] The cells may be stem cells.
[0616] The cells may be pluripotent stem cells.
[0617] According to an embodiment of the present invention, HLA-A * 11:01g, HLA-C * 01:02g, HLA-B * 54:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:05, and HLA-DQB1* Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 04:01g.
[0618] The cells may be stem cells.
[0619] The cells may be pluripotent stem cells.
[0620] According to an embodiment of the present invention, HLA-A * Cells homozygous for 11:01g are provided.
[0621] The above cells are HLA-C * They may be homozygous for 01:02g.
[0622] The above cells are HLA-B * 54:01g may be homozygous.
[0623] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0624] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0625] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0626] The cells may be stem cells.
[0627] The cells may be pluripotent stem cells.
[0628] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 01:02g are provided.
[0629] The above cells are HLA-B * 54:01g may be homozygous.
[0630] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0631] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0632] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0633] The cells may be stem cells.
[0634] The cells may be pluripotent stem cells.
[0635] According to an embodiment of the present invention, HLA-B * Cells homozygous for 54:01g are provided.
[0636] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0637] The above cells are HLA-DRB1 * The patient may be homozygous for 04:05.
[0638] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0639] The cells may be stem cells.
[0640] The cells may be pluripotent stem cells.
[0641] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0642] The above cells are HLA-DRB1* The patient may be homozygous for 04:05.
[0643] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0644] The cells may be stem cells.
[0645] The cells may be pluripotent stem cells.
[0646] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 04:05 are provided.
[0647] The above cells are HLA-DQB1 * 04:01g may be homozygous.
[0648] The cells may be stem cells.
[0649] The cells may be pluripotent stem cells.
[0650] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 04:01g are provided.
[0651] The cells may be stem cells.
[0652] The cells may be pluripotent stem cells.
[0653] According to an embodiment of the present invention, HLA-A * 26:01g, HLA-C * 03:04g, HLA-B * 40:02g, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 03:03g.
[0654] The cells may be stem cells.
[0655] The cells may be pluripotent stem cells.
[0656] According to an embodiment of the present invention, HLA-A * Cells homozygous for 26:01g are provided.
[0657] The above cells are HLA-C * 03:04g may be homozygous.
[0658] The above cells are HLA-B * They may be homozygous for 40:02g.
[0659] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0660] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0661] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0662] The cells may be stem cells.
[0663] The cells may be pluripotent stem cells.
[0664] According to an embodiment of the present invention, HLA-C * Cells homozygously carrying 03:04g are provided.
[0665] The above cells are HLA-B * They may be homozygous for 40:02g.
[0666] The above cells are HLA-DRB4 *The patient may be homozygous for 01:01g.
[0667] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0668] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0669] The cells may be stem cells.
[0670] The cells may be pluripotent stem cells.
[0671] According to an embodiment of the present invention, HLA-B * Cells homozygous for 40:02g are provided.
[0672] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0673] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0674] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0675] The cells may be stem cells.
[0676] The cells may be pluripotent stem cells.
[0677] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0678] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0679] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0680] The cells may be stem cells.
[0681] The cells may be pluripotent stem cells.
[0682] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 09:01 are provided.
[0683] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0684] The cells may be stem cells.
[0685] The cells may be pluripotent stem cells.
[0686] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 03:03g are provided.
[0687] The cells may be stem cells.
[0688] The cells may be pluripotent stem cells.
[0689] According to an embodiment of the present invention, HLA-A * 24:02g, HLA-C * 08:01g, HLA-B * 40:06, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * Cells are provided that are homozygous for at least one, two, three, four, or all of the group consisting of 03:03g.
[0690] The cells may be stem cells.
[0691] The cells may be pluripotent stem cells.
[0692] According to an embodiment of the present invention, HLA-A * Cells homozygous for 24:02g are provided.
[0693] The above cells are HLA-C * They may be homozygous for 08:01g.
[0694] The above cells are HLA-B * The patient may be homozygous for 40:06.
[0695] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0696] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0697] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0698] The cells may be stem cells.
[0699] The cells may be pluripotent stem cells.
[0700] According to an embodiment of the present invention, HLA-C * Cells homozygous for 08:01g are provided.
[0701] The above cells are HLA-B * The patient may be homozygous for 40:06.
[0702] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0703] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0704] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0705] The cells may be stem cells.
[0706] The cells may be pluripotent stem cells.
[0707] According to an embodiment of the present invention, HLA-B * Cells homozygous for 40:06 are provided.
[0708] The above cells are HLA-DRB4 * The patient may be homozygous for 01:01g.
[0709] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0710] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0711] The cells may be stem cells.
[0712] The cells may be pluripotent stem cells.
[0713] According to an embodiment of the present invention, HLA-DRB4 * Cells homozygous for 01:01g are provided.
[0714] The above cells are HLA-DRB1 * The patient may be homozygous for 09:01.
[0715] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0716] The cells may be stem cells.
[0717] The cells may be pluripotent stem cells.
[0718] According to an embodiment of the present invention, HLA-DRB1 * Cells homozygous for 09:01 are provided.
[0719] The above cells are HLA-DQB1 * 03:03g may be homozygous.
[0720] The cells may be stem cells.
[0721] The cells may be pluripotent stem cells.
[0722] According to an embodiment of the present invention, HLA-DQB1 * Cells homozygous for 03:03g are provided.
[0723] The cells may be stem cells.
[0724] The cells may be pluripotent stem cells.
[0725] According to an embodiment of the present invention, HLA-A * 02:01, HLA-C * 06:02, and HLA-DPA1 * Cells are provided that are homozygous for at least one, two, or all of the group consisting of: 01:03.
[0726] The cells may be stem cells.
[0727] The cells may be pluripotent stem cells.
[0728] According to an embodiment of the present invention, HLA-A * Cells homozygous for 02:01 are provided.
[0729] The above cells are HLA-C * The patient may be homozygous for 06:02.
[0730] The above cells are HLA-DPA1 * The patient may be homozygous for 01:03.
[0731] The cells may be stem cells.
[0732] The cells may be pluripotent stem cells.
[0733] According to an embodiment of the present invention, HLA-C * Cells homozygous for 06:02 are provided.
[0734] The above cells are HLA-DPA1 * The patient may be homozygous for 01:03.
[0735] The cells may be stem cells.
[0736] The cells may be pluripotent stem cells.
[0737] According to an embodiment of the present invention, HLA-DPA1 * Cells homozygous for 01:03 are provided.
[0738] The cells may be stem cells.
[0739] The cells may be pluripotent stem cells. [Effects of the Invention]
[0740] According to the present invention, it is possible to provide cells that cause less rejection when transplanted. [Brief explanation of the drawings]
[0741] [Figure 1]1 is a table showing combinations of HLA haplotype homozygotes in Caucasian donors according to Example 1. [Figure 2] 1 is a table showing the allele frequencies of each of the Caucasian donors according to Example 1. [Figure 3] 1 is a table showing the allele frequencies of each of the Caucasian donors according to Example 1. [Figure 4] 1 is a table showing combinations of HLA haplotype homozygotes in Japanese people according to Example 3. [Figure 5] 1 is a table showing the allele frequencies of each of the Japanese donors according to Example 3. [Figure 6] 1 is a table showing the allele frequencies of each of the Caucasian donors according to Example 5. DETAILED DESCRIPTION OF THE INVENTION
[0742] The following describes embodiments of the present invention. However, it should not be understood that the following embodiments limit the present invention. From this disclosure, various alternative embodiments, examples, and operating techniques will become apparent to those skilled in the art. It should be understood that the present invention encompasses various embodiments not described herein.
[0743] The cells according to the first embodiment are HLA-A * 01:01g, HLA-B * 08:01g, and HLA-DRB1 * Homozygous for 03:01. HLA-A * 01:01g, HLA-B * 08:01g, and HLA-DRB1 * Cells homozygous for 03:01 are HLA-C * 07:01g may be homozygous, and HLA-DQB1 * 02:01g may be homozygous, and HLA-DRB3 * The patient may have 01:01 homozygously.
[0744] The cells according to the second embodiment are HLA-A * 03:01g, HLA-B * 07:02g, and HLA-DRB1 * Homozygous for 15:01. HLA-A * 03:01g, HLA-B * 07:02g, and HLA-DRB1 * Cells homozygous for 15:01 are HLA-C * 07:02g may be homozygous, and HLA-DQB1 * 06:02 homozygous, HLA-DRB5 * The patient may have 01:01 homozygously.
[0745] The cells according to the third embodiment are HLA-A * 02:01g, HLA-B * 07:02g, and HLA-DRB1 * Homozygous for 15:01. HLA-A * 02:01g, HLA-B * 07:02g, and HLA-DRB1 * Cells homozygous for 15:01 are HLA-C * 07:02g may be homozygous, and HLA-DQB1 * 06:02 homozygous, HLA-DRB5 * The patient may have 01:01 homozygously.
[0746] The cells according to the fourth embodiment are HLA-A * 02:01g, HLA-B * 44:02g, and HLA-DRB1 * Homozygous for 04:01. HLA-A * 02:01g, HLA-B * 44:02g, and HLA-DRB1 * Cells homozygous for 04:01 are HLA-C * 05:01g may be homozygous, and HLA-DQB1 * 03:01g may be homozygous, and HLA-DRB4 *The patient may be homozygous for 01:01g.
[0747] The cells according to the fifth embodiment are HLA-A * 29:02g, HLA-B * 44:03, and HLA-DRB1 * Homozygous for 07:01. HLA-A * 29:02g, HLA-B * 44:03, and HLA-DRB1 * Cells homozygous for 07:01 are HLA-C * 16:01 homozygous, HLA-DQB1 * 02:01g may be homozygous, and HLA-DRB4 * The patient may be homozygous for 01:01g.
[0748] The cells according to the sixth embodiment are HLA-A * 03:01g, HLA-B * 35:01g, and HLA-DRB1 * Homozygous for 01:01. HLA-A * 03:01g, HLA-B * 35:01g, and HLA-DRB1 * Cells homozygous for 01:01 are HLA-C * 04:01g may be homozygous, and HLA-DQB1 * 05:01 homozygous, HLA-DRBX * The patient may have homozygous NNNN.
[0749] The cells according to the seventh embodiment are HLA-A * 02:01g, HLA-B * 08:01g, and HLA-DRB1 * Homozygous for 03:01. HLA-A * 02:01g, HLA-B * 08:01g, and HLA-DRB1 * Cells homozygous for 03:01 are HLA-C * 07:01g may be homozygous, and HLA-DQB1* 02:01g may be homozygous, and HLA-DRB3 * The patient may have 01:01 homozygously.
[0750] The cells according to the eighth embodiment are HLA-A * 01:01g, HLA-B * 57:01g, and HLA-DRB1 * Homozygous for 07:01. HLA-A * 01:01g, HLA-B * 57:01g, and HLA-DRB1 * Cells homozygous for 07:01 are HLA-C * 06:02g may be homozygous, and HLA-DQB1 * 03:03g may be homozygous, and HLA-DRB4 * The patient may be homozygous for 01:01g.
[0751] The cells according to the ninth embodiment are HLA-A * 02:01g, HLA-B * 40:01g, and HLA-DRB1 * Homozygous for 13:02. HLA-A * 02:01g, HLA-B * 40:01g, and HLA-DRB1 * Cells homozygous for 13:02 are HLA-C * 03:04g may be homozygous, and HLA-DQB1 * 06:04g may be homozygous, and HLA-DRB3 * The patient may be homozygous for 03:01.
[0752] The cells according to the tenth embodiment are HLA-A * 24:02g, HLA-B * 07:02g, and HLA-DRB1 * Homozygous for 15:01. HLA-A * 24:02g, HLA-B * 07:02g, and HLA-DRB1 *Cells homozygous for 15:01 are HLA-C * 07:02g may be homozygous, and HLA-DQB1 * 06:02 homozygous, HLA-DRB5 * The patient may have 01:01 homozygously.
[0753] In a Caucasian population, the frequency of each allele combination in the cells according to the first to tenth embodiments is high. For example, in a Caucasian population, the frequency of each allele combination in the cells according to the first to tenth embodiments is 2.0% or more, 2.5% or more, 3.0% or more, 3.5% or more, 4.0% or more, 4.5% or more, 5.0% or more, 5.5% or more, 6.0% or more, 6.5% or more, 7.0% or more, 7.5% or more, 8.0% or more, 8.5% or more, 9.0% or more, 9.5% or more , 10.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 17.0% or more, 18.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 18.0% or more, 20.0% or more, 22.0% or more, 24.0% or more, or 26.0% or more. Therefore, the cells according to the first to tenth embodiments are suitable for transplantation into Caucasians. Furthermore, by combining at least any of the cells according to the first to tenth embodiments, it is possible to cover a large number of Caucasians.
[0754] The cells according to the eleventh embodiment are HLA-A * 24:02g, HLA-B * 52:01g, and HLA-DRB1 * Homozygous for 15:02. HLA-A * 24:02g, HLA-B * 52:01g, and HLA-DRB1 * Cells homozygous for 15:02 are HLA-C * 12:02 homozygous, HLA-DRB5 * 01:02g may be homozygous, and HLA-DQB1 *The patient may be homozygous for 06:01.
[0755] The cells according to the twelfth embodiment are HLA-A * 33:03g, HLA-B * 44:03, and HLA-DRB1 * Homozygous for 13:02. HLA-A * 33:03g, HLA-B * 44:03, and HLA-DRB1 * Cells homozygous for 13:02 are HLA-C * 14:03 may be homozygous, and HLA-DRB3 * 03:01 homozygous, and HLA-DQB1 * They may be homozygous for 06:04g.
[0756] The cells according to the thirteenth embodiment are HLA-A * 24:02g, HLA-B * 07:02g, and HLA-DRB1 * Homozygous for 01:01. HLA-A * 24:02g, HLA-B * 07:02g, and HLA-DRB1 * Cells homozygous for 01:01 are HLA-C * 07:02g may be homozygous, and HLA-DRBX * NNNN homozygous, HLA-DQB1 * The patient may be homozygous for 05:01.
[0757] The cells according to the fourteenth embodiment are HLA-A * 24:02g, HLA-B * 54:01g, and HLA-DRB1 * Homozygous for 04:05. HLA-A * 24:02g, HLA-B * 54:01g, and HLA-DRB1 * Cells homozygous for 04:05 are HLA-C *01:02g may be homozygous, and HLA-DRB4 * 01:01g may be homozygous, and HLA-DQB1 * 04:01g may be homozygous.
[0758] The cells according to the fifteenth embodiment are HLA-A * 24:02g, HLA-B * 59:01, and HLA-DRB1 * Homozygous for 04:05. HLA-A * 24:02g, HLA-B * 59:01, and HLA-DRB1 * Cells homozygous for 04:05 are HLA-C * 01:02g may be homozygous, and HLA-DRB4 * 01:01g may be homozygous, and HLA-DQB1 * 04:01g may be homozygous.
[0759] The cells according to the sixteenth embodiment are homozygous for HLA-A*02:07g, HLA-B*46:01g, and HLA-DRB1*08:03. Cells homozygous for HLA-A*02:07g, HLA-B*46:01g, and HLA-DRB1*08:03 may also be homozygous for HLA-C*01:02g, homozygous for HLA-DRBX*NNNN, or homozygous for HLA-DQB1*06:01.
[0760] In the Japanese population, the frequency of each allele combination of the cells according to embodiments 11 to 20 is high. For example, in the Japanese population, the frequency of each allele combination of the cells according to embodiments 11 to 20 is 2.0% or more, 2.5% or more, 3.0% or more, 3.5% or more, 4.0% or more, 4.5% or more, 5.0% or more, 5.5% or more, 6.0% or more, 6.5% or more, 7.0% or more, 7.5% or more, 8.0% or more, 8.5% or more, 9.0% or more, 9.5% or more, 10. 0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 17.0% or more, 18.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 18.0% or more, 20.0% or more, 22.0% or more, 24.0% or more, 26.0% or more, or 27.0%. Therefore, the cells according to the 11th to 20th embodiments are suitable for transplantation into Japanese people. Furthermore, by combining at least any of the cells according to the 11th to 20th embodiments, it is possible to cover a large number of Japanese people.
[0761] The cells according to the 21st embodiment are HLA-A * 02:01, HLA-C * 06:02, and HLA-DPA1 * He is homozygous for 01:03.
[0762] In a Caucasian population, the frequency of the allele combination of the cells according to the 21st embodiment is high. For example, in a Caucasian population, the frequency of the allele combination of the cells according to the 21st embodiment is 2.0% or more, 2.5% or more, 3.0% or more, 3.5% or more, 4.0% or more, 4.5% or more, 5.0% or more, 5.5% or more, 6.0% or more, 6.5% or more, 7.0% or more, 7.5% or more, 8.0% or more, 8.5% or more, 9.0% or more, 9.5% or more, 10. 0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 17.0% or more, 18.0% or more, 11.0% or more, 12.0% or more, 13.0% or more, 14.0% or more, 15.0% or more, 16.0% or more, 18.0% or more, 20.0% or more, 22.0% or more, 24.0% or more, or 26.0% or more. Therefore, the cells according to the 21st embodiment are suitable for transplantation into Caucasians.
[0763] The cells according to the first to twenty-first embodiments may be derived from a human or a non-human animal. The cells according to the first to twenty-first embodiments may be somatic cells. Examples of somatic cells include, but are not limited to, fibroblasts, blood cells, dental pulp stem cells, keratinocytes, hair papilla cells, oral epithelial cells, somatic stem progenitor cells, and urinary cells. The blood cells may be nucleated cells such as monocytes, neutrophils, eosinophils, basophils, and lymphocytes. The blood cells may be, for example, endothelial progenitor cells, blood stem / progenitor cells, T cells, or B cells. The T cells may be, for example, αβ T cells or γδ T cells. The blood cells may also be blood cells that do not contain T cells.
[0764] The cells according to the first to twenty-first embodiments may be stem cells. The stem cells may be pluripotent stem cells. Pluripotent stem cells have a positivity rate of 30% or more, 50% or more, and preferably 80% or more for any of TRA1-60, OCT3 / 4, SSEA3, SSEA4, TRA1-81, LIN28, and NANOG, for example. Examples of pluripotent stem cells include iPS cells and embryonic stem cells (ES cells). iPS cells are induced by introducing an inducer into somatic cells. In inducing stem cells, induction refers to reprogramming, reprogramming, transformation, cell fate reprogramming, etc.
[0765] Examples of inducers include OCT3 / 4, SOX2, KLF4, and c-MYC. M3O, an improved version of OCT3 / 4, may also be used as the inducer. The inducer may also be at least one selected from the group consisting of LIN28A, FOXH1, LIN28B, GLIS1, p53-dominant negative, p53-P275S, L-MYC, NANOG, DPPA2, DPPA4, DPPA5, ZIC3, BCL-2, E-RAS, TPT1, SALL2, NAC1, DAX1, TERT, ZNF206, FOXD3, REX1, UTF1, KLF2, KLF5, ESRRB, miR-291-3p, miR-294, miR-295, NR5A1, NR5A2, TBX3, MBD3sh, TH2A, TH2B, and P53DD. These inducer RNAs are available from TriLink. Note that although gene symbols are written in human form here, capitalization is not intended to limit species. For example, even if all letters are used, it does not exclude the inclusion of mouse or rat genes. However, in the examples, gene symbols are written according to the species actually used.
[0766] The inducer may be RNA. The RNA may be mRNA. The inducer RNA may be selected from the group consisting of pseudouridine (Ψ), 5-methyluridine (5meU), N1-methylpseudouridine (melΨ), 5-methoxyuridine (5moU), 5-hydroxymethyluridine (5hmU), 5-formyluridine (5fU), 5-carboxymethylesteruridine (5camU), thienoguanosine (thG), N4-methylcytidine (me4C), 5-methylcytidine (m5C), 5-methyoxycytidine (5moC), 5-hydroxymethyl ...hydroxymethyluridine (5camU), thienoguanosine (thG), N4-methylcytidine (me4C), 5-methylcytidine (m5C), 5-hydroxymethyluridine (5camU), thienoguanosine (thG), N4-methylcytidine (me4C), 5-hydroxymethyluridine (m5C), 5-hydroxymethyluridine (5camU), thienoguanosine (thG), N4-methylcytidine (me4C), 5-hydroxymethyluridine (m5C), 5-hydroxymethyluridine (5camU), thienoguanosine (thG), N4-methylcytidine (me4C), 5- The inducer RNA may be modified with at least one selected from the group consisting of 5-methylcytidine (5hmC), 5-hydroxycytidine (5hoC), 5-formcytidine (5fC), 5-carboxycytidine (5caC), N6-methyl-2-aminoadenosine (m6DAP), diaminopurine (DAP), 5-methyluridine (m5U), 2'-O-methyluridine (Um or m2'-OU), 2-thiouridine (s2U), and N6-methyladenosine (m6A). The inducer RNA may be polyadenylated.
[0767] The inducer is introduced into cells, for example, by lipofection. Lipofection is a method in which a complex of a negatively charged substance, nucleic acid, and a positively charged lipid, is formed by electrical interaction, and the complex is taken up into cells by endocytosis or membrane fusion. The lipofection method has advantages such as minimal damage to cells, excellent introduction efficiency, simple operation, and short time required.
[0768] The inducer is introduced into the cultured cells using, for example, an RNA transfection reagent. For example, if the cells are mononuclear cells, the RNA may be introduced into the mononuclear cells immediately after isolating them from blood.
[0769] Alternatively, an inducer is introduced into cells using, for example, a viral vector. The viral vector may be an RNA viral vector. By using an RNA viral vector, cells can be induced without integration. The RNA viral vector may be a single-stranded positive-strand RNA virus. The RNA viral vector may be a single-stranded negative-strand RNA virus. The RNA viral vector may be a Sendai virus vector, a retroviral vector, a lentiviral vector, or a rubella virus vector. The Sendai virus vector may be a temperature-sensitive Sendai virus vector in which the stability of the viral nucleic acid decreases above a certain temperature. The viral nucleic acid of a temperature-sensitive Sendai virus vector is stable below a certain temperature. The viral nucleic acid may be viral DNA or viral RNA. The viral nucleic acid may be a viral genome. The decrease in stability of the viral nucleic acid may be at least one of degradation of the viral nucleic acid and inhibition of replication or proliferation of the viral nucleic acid. The decrease in stability of the viral nucleic acid results in a decrease in at least one of proliferation of the viral nucleic acid, the replication rate of the viral nucleic acid, and the gene expression level. Examples of the predetermined temperature include 36.5°C to 37.5°C, 36.6°C to 37.4°C, 36.7°C to 37.3°C, 36.8°C to 37.2°C, 36.9°C to 37.1°C, and 37°C. The stability of the viral nucleic acid of a temperature-sensitive Sendai virus vector, i.e., at least one of the growth, replication rate, and gene expression level, is high below the predetermined temperature and low above the predetermined temperature. For example, the growth rate or gene expression level of a temperature-sensitive Sendai virus vector in cells cultured at 37°C is at most 1 / 2, 1 / 3, 1 / 5, 1 / 10, or 1 / 20 of that in cells cultured at 32°C.
[0770] After introducing an inducer into the cells and culturing the cells, all the cells into which the inducer has been introduced are passaged at least once. Thereafter, all the cells into which the inducer has been introduced may be passaged multiple times. All the cells into which the inducer has been introduced may be passaged until stem cells are established.
[0771] Here, "passaging all cells into which an inducer has been introduced" refers to, for example, passaging the cells into which an inducer has been introduced without distinguishing them based on their gene expression state. For example, during passaging, the cells into which an inducer has been introduced may be seeded in the same culture vessel without distinguishing them based on their gene expression state. Alternatively, "passaging all cells into which an inducer has been introduced" refers to, for example, passaging the cells into which an inducer has been introduced without distinguishing them based on the degree of reprogramming. For example, during passaging, the cells into which an inducer has been introduced may be seeded in the same culture vessel without distinguishing them based on the degree of reprogramming.
[0772] Alternatively, "passaging all cells into which an inducer has been introduced" refers to, for example, passaging the cells into which an inducer has been introduced without distinguishing them by morphology. For example, during passaging, the cells into which an inducer has been introduced may be seeded in the same culture vessel without distinguishing them by morphology. Alternatively, "passaging all cells into which an inducer has been introduced" refers to, for example, passaging the cells into which an inducer has been introduced without distinguishing them by size. For example, during passaging, the cells into which an inducer has been introduced may be seeded in the same culture vessel without distinguishing them by size.
[0773] Alternatively, passaging all cells into which an inducer has been introduced refers to passaging the cells into which an inducer has been introduced without cloning. For example, when passaging without cloning, it is not necessary to pick up colonies formed by cells into which an inducer has been introduced. For example, when passaging without cloning, it is not necessary to separate multiple colonies formed by cells into which an inducer has been introduced. For example, when passaging without cloning, it is not necessary to separate multiple colonies formed by cells into which an inducer has been introduced. For example, when passaging without cloning, it is not necessary to clone a single colony formed by cells into which an inducer has been introduced. For example, when passaging, it is not necessary to mix colonies and seed them in the same culture vessel.
[0774] For example, when cells into which an inducer has been introduced are cultured in adhesion, the entire adherent cultured cells may be passaged. For example, when passaging, all cells detached from the culture vessel may be seeded in the same culture vessel. For example, all cells detached from the culture vessel may be passaged using a detachment solution. For example, cells that have not formed colonies may be passaged. When cells into which an inducer has been introduced are cultured in suspension, the entire suspension cultured cells may be passaged.
[0775] When cells into which an inducer has been introduced are subcultured, the cells are seeded in a medium or culture vessel at a low density. Here, a low density means, for example, 1 cell / cm. 2 or more, 0.25 x 10 4 cells / cm 2 Below, 1.25 x 10 3 cells / cm 2 Below, 0.25 x 10 3 cells / cm 2 Below, 0.25 x 10 2 cells / cm 2 or less, or 0.25 x 10 1 cells / cm 2or less. Alternatively, a low concentration refers to a concentration at which 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less cells can contact each other, but 11 or more cells do not contact each other. Note that there may be multiple cell clumps in which 10 or less cells are in contact with each other. Alternatively, a state in which the entire bottom surface of the cell container is covered with cells is considered to be 100% confluent, and a low concentration refers to 5% or less confluent, 4% or less confluent, 3% or less confluent, 2% or less confluent, 1% or less confluent, 0.5% or less confluent, 0.1% or less confluent, 0.05% or less confluent, or 0.01% or less confluent. Alternatively, a low concentration refers to a concentration at which single cells do not contact each other among the seeded cells. For example, single cells may be seeded into the wells of a well plate. The well plate may be a 12-well plate or a 96-well plate. According to the findings of the present inventors, when cells into which an inducer has been introduced are passaged, seeding the cells in a medium at a low concentration makes it possible to suppress the persistence of Sendai virus in pluripotent stem cells induced from the cells. The percentage of cells in which Sendai virus persists among the induced pluripotent stem cells is, for example, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0%.
[0776] The cells according to the first to twenty-first embodiments may be somatic cells differentiated from stem cells. Examples of somatic cells differentiated from stem cells include, but are not limited to, nerve cells, neural stem cells, retinal cells, corneal cells, cardiac muscle cells, muscle cells, chondrocytes, immune cells, pancreatic beta cells, fibroblasts, blood cells, dental pulp stem cells, keratinocytes, hair papilla cells, oral epithelial cells, somatic stem progenitor cells, and urinary cells. The blood cells may be nucleated cells, red blood cells, granulocytes, and platelets.
[0777] Neuronal cells are suitable for transplantation into patients with Parkinson's disease, for example. Retinal cells and corneal cells are suitable for transplantation into patients with eye diseases, for example. Cardiomyocytes are suitable for transplantation into patients with heart failure, for example. Neural stem cells are suitable for transplantation into patients with spinal cord injuries, for example. Platelets are suitable for transfusions, for example. Immune cells are suitable for transplantation into cancer patients, for example. Pancreatic beta cells are suitable for transplantation into patients with diabetes, for example. Chondrocytes are suitable for transplantation into patients with joint diseases, for example. [Example]
[0778] Example 1: Matching rate of Caucasian HLA homozygous donors In the following, allele frequencies were calculated using the database (http: / / www.allelefrequencies.net / hla6003a.asp) with all Caucasian HLA types as the denominator. As shown in Figures 1, 2, and 3, HLA-A * 01:01g, HLA-B * 08:01g, HLA-C * 07:01g, HLA-DRB1 * 03:01, HLA-DQB1 * 02:01g, and HLA-DRB3 * Cells from Caucasian donor 1, homozygous for 01:01, were calculated to match 26.119% of 310,739 randomly selected Caucasians and 16.893% of 584,482 randomly selected Americans.
[0779] HLA-A * 03:01g, HLA-B * 07:02g, HLA-C * 07:02g, HLA-DRB1 * 15:01, HLA-DQB1 * 06:02, and HLA-DRB5 *Cells from Caucasian donor 2, homozygous for 01:01, were calculated to match 12.439% of 310,739 randomly selected Caucasians and 8.510% of 584,482 randomly selected Americans.
[0780] HLA-A * 02:01g, HLA-B * 07:02g, HLA-C *0 7:02g, HLA-DRB1 * 15:01, HLA-DQB1 * 06:02, and HLA-DRB5 * Cells from Caucasian donor 3, homozygous for 01:01, were calculated to match 7.880% of 310,739 randomly selected Caucasians and 5.160% of 584,482 randomly selected Americans.
[0781] HLA-A * 02:01g, HLA-B * 44:02g, HLA-C * 05:01g, HLA-DRB1 * 04:01, HLA-DQB1 * 03:01g, and HLA-DRB4 * Cells from Caucasian donor 4, homozygous for each of the 01:01g alleles, were calculated to match 7.400% of 310,739 randomly selected Caucasians and 4.667% of 584,482 randomly selected Americans.
[0782] HLA-A * 29:02g, HLA-B * 44:03, HLA-C * 16:01, HLA-DRB1 * 07:01, HLA-DQB1 * 02:01g, and HLA-DRB4 *Cells from Caucasian donor 5, homozygous for each of the 01:01g genes, were calculated to match 6.280% of 310,739 randomly selected Caucasians and 5.439% of 584,482 randomly selected Americans.
[0783] HLA-A * 03:01g, HLA-B * 35:01g, HLA-C * 04:01g, HLA-DRB1 * 01:01, HLA-DQB1 * 05:01, and HLA-DRBX * Cells from Caucasian donor 6, homozygous for each of the NNNN genes, were calculated to match 4.480% of 310,739 randomly selected Caucasians and 3.223% of 584,482 randomly selected Americans.
[0784] HLA-A * 02:01g, HLA-B * 08:01g, HLA-C * 07:01g, HLA-DRB1 * 03:01, HLA-DQB1 * 02:01g, and HLA-DRB3 * Cells from Caucasian donor 7, homozygous for 01:01, were calculated to match 3.440% of 310,739 randomly selected Caucasians and 2.250% of 584,482 randomly selected Americans.
[0785] HLA-A * 01:01g, HLA-B * 57:01g, HLA-C * 06:02g, HLA-DRB1 * 07:01, HLA-DQB1 * 03:03g, and HLA-DRB4 *Cells from Caucasian donor 8, homozygous for each of the 01:01g alleles, were calculated to match 3.320% of 310,739 randomly selected Caucasians and 2.903% of 584,482 randomly selected Americans.
[0786] HLA-A * 02:01g, HLA-B * 40:01g, HLA-C * 03:04g, HLA-DRB1 * 13:02, HLA-DQB1 * 06:04g, and HLA-DRB3 * Cells from Caucasian donor 9, homozygous for each of the 03:01 mutations, were calculated to match 3.080% of 310,739 randomly selected Caucasians and 1.922% of 584,482 randomly selected Americans.
[0787] HLA-A * 24:02g, HLA-B * 07:02g, HLA-C * 07:02g, HLA-DRB1 * 15:01, HLA-DQB1 * 06:02, and HLA-DRB5 * Cells from 10 Caucasian donors homozygous for 01:01 were calculated to match 2.920% of 310,739 randomly selected Caucasians and 2.107% of 584,482 randomly selected Americans.
[0788] Example 2: Production of iPS cells from Caucasian donors A serum-free and animal-derived component-free hematopoietic cell culture medium (Stemspan ACF, STEMCELL TECHNOLOGIES) was supplemented with recombinant protein FLT3 ligand (PEPROTECH), recombinant human TPO (PEPROTECH), recombinant human IL-6 (PEPROTECH), recombinant human G-CSF (PEPROTECH), and recombinant human SCF (PEPROTECH) to prepare a hematopoietic cell culture medium. 2 × 10 cells were added to each well of a 12-well dish. 5 Blood cells (peripheral blood mononuclear cells) derived from Caucasian donor 1 according to Example 1 were seeded on the wells of the 12-well dish. The 12-well dish was then placed in a CO2 incubator at 37°C to culture the cells in suspension and expand the non-T cells.
[0789] Three days after the start of cell culture, hematopoietic cell medium was added to each well as needed. Six days after the start of cell culture, Oct3 / 4, SOX2, KLF4, and c-Myc were transfected into the cells in each well, after which hematopoietic cell medium was added to each well and the cells were cultured on laminin 511-coated dishes, a stem cell culture substrate. Starting two days after infection, half of the culture medium in each well was replaced with stem cell medium every two days. 14 days after infection, it was confirmed that 10 or more iPS cell clusters had been induced. iPS cells were also induced in a similar manner from blood cells from Caucasian donors 2, 3, 4, 5, 6, 7, 8, 9, and 10 of Example 1.
[0790] (Example 3: Matching rate of Japanese HLA-homologous donors) In the following, the allele frequencies were calculated using the database (http: / / www.allelefrequencies.net / hla6003a.asp) with all HLA types in Japanese people as the denominator. As shown in Figures 4 and 5, * 24:02g, HLA-C * 12:02, HLA-B * 52:01g, HLA-DRB5 * 01:02g, HLA-DRB1 *15:02, and HLA-DQB1 * Cells from Japanese donor 1, who is homozygous for each of the 06:01 mutations, were calculated to match 27.161% of 7,080 randomly selected Japanese individuals.
[0791] HLA-A * 33:03g, HLA-C * 14:03, HLA-B * 44:03, HLA-DRB3 * 03:01, HLA-DRB1 * 13:02, and HLA-DQB1 * Cells from Japanese donor 2, who is homozygous for each of the 06:04g genes, were calculated to match 13.658% of 7,080 randomly selected Japanese individuals.
[0792] HLA-A * 24:02g, HLA-C * 07:02g, HLA-B * 07:02g, HLA-DRBX * NNNN, HLA-DRB1 * 01:01, and HLA-DQB1 * Cells from Japanese donor 3, who is homozygous for each of the 05:01 mutations, were calculated to match 12.232% of 7,080 randomly selected Japanese individuals.
[0793] HLA-A * 24:02g, HLA-C * 01:02g, HLA-B * 54:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:05, and HLA-DQB1 * Cells from Japanese donor 4, who is homozygous for each of the 04:01g alleles, were calculated to match 8.997% of 7,080 randomly selected Japanese individuals.
[0794] HLA-A * 24:02g, HLA-C * 01:02g, HLA-B *59:01, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:05, and HLA-DQB1 * Cells from Japanese donor 5, who is homozygous for each of the 04:01g alleles, were calculated to match 4.732% of 7,080 randomly selected Japanese individuals.
[0795] HLA-A * 02:07g, HLA-C * 01:02g, HLA-B * 46:01g, HLA-DRBX * NNNN, HLA-DRB1 * 08:03, and HLA-DQB1 * Cells from Japanese donor 6, who is homozygous for each of the 06:01 mutations, were calculated to match 4.209% of 7,080 randomly selected Japanese individuals.
[0796] HLA-A * 11:01g, HLA-C * 04:01g, HLA-B * 15:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:06, and HLA-DQB1 * Cells from Japanese donor 7, who is homozygous for each of the 03:02g alleles, were calculated to match 3.658% of 7,080 randomly selected Japanese individuals.
[0797] HLA-A * 11:01g, HLA-C * 01:02g, HLA-B * 54:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:05, and HLA-DQB1 * Cells from Japanese donor 8, who was homozygous for each of the 04:01g alleles, were calculated to match 3.588% of 7,080 randomly selected Japanese individuals.
[0798] HLA-A *26:01g, HLA-C * 03:04g, HLA-B * 40:02g, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * Cells from Japanese donor 9, who was homozygous for each of the 03:03g alleles, were calculated to match 3.376% of 7,080 randomly selected Japanese individuals.
[0799] HLA-A * 24:02g, HLA-C * 08:01g, HLA-B * 40:06, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * Cells from 10 Japanese donors homozygous for each of the 03:03g genes were calculated to match 2.994% of 7,080 randomly selected Japanese individuals.
[0800] Example 4: Production of iPS cells from Japanese donors Using a method similar to that used in Example 2, iPS cells were induced from the blood cells of Japanese donors 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 of Example 3.
[0801] Example 5: Matching rate of HLA-homologous donors in the United States Allele frequencies were calculated using the database (http: / / www.allelefrequencies.net / hla6003a.asp) with all HLA types in the US population as the denominator. * Cells from an American donor homozygous for HLA-C*02:01 were calculated to match 35.9% of randomly selected Americans. Cells from an American donor homozygous for HLA-C*06:02 were calculated to match 61.0% of randomly selected Americans. As shown in Figure 6, HLA-A *Cells from an American donor homozygous for HLA-C*02:01 were calculated to match 32.434% of randomly selected Caucasians. Cells from an American donor homozygous for HLA-C*06:02 were calculated to match 10.173% of randomly selected Caucasians. HLA-A * Cells from an American donor homozygous for HLA-C*02:01 and HLA-C*06:02 were calculated to be a match for 30.13% of randomly selected Caucasians.
[0802] Example 6: Production of iPS cells from American donors Using the same method as in Example 2, iPS cells were induced from blood cells of an American donor who was homozygous for HLA-A*02:01, HLA-C*06:02, and HLA-DPA1*01:03.
Claims
【Request Item 1】 HLA-A * 01:01g, HLA-B * 08:01g, HLA-DRB1 * 03:01, HLA-C * 07:01g, HLA-DQB1 * 02:01g, and HLA-DRB3 * 01:
01. A cell homozygously having at least one, two, three, four, or all of the group consisting of: 【Request Item 2】 HLA-A * 03:01g, HLA-B * 07:02g, HLA-DRB1 * 15:01, HLA-C * 07:02g, HLA-DQB1 * 06:02, and HLA-DRB5 * 01:
01. A cell homozygously having at least one, two, three, four, or all of the group consisting of: 【Request Item 3】 HLA-A * 02:01g, HLA-B * 07:02g, HLA-DRB1 * 15:01, HLA-C * 07:02g, HLA-DQB1 * 06:02, and HLA-DRB5 * 01:
01. A cell homozygously having at least one, two, three, four, or all of the group consisting of: 【Request Item 4】 HLA-A * 02:01g, HLA-B * 44:02g, HLA-DRB1 * 04:01, HLA-C * 05:01g, HLA-DQB1 * 03:01g, and HLA-DRB4 * 01:01g. A cell homozygously comprising at least one, two, three, four, or all of the following: 【Request Item 5】 HLA-A * 29:02g, HLA-B * 44:03, HLA-DRB1 * 07:01, HLA-C * 16:01, HLA-DQB1 * 02:01g, and HLA-DRB4 * 01:01g. A cell homozygously comprising at least one, two, three, four, or all of the following: 【Request Item 6】 HLA-A * 03:01g, HLA-B * 35:01g, HLA-C * 04:01g, HLA-DRB1 * 01:01, HLA-DQB1 * 05:01, and HLA-DRBX * A cell homozygous for at least one, two, three, four, or all of the group consisting of: NNNN. 【Request Item 7】 HLA-A * 02:01g, HLA-B * 08:01g, HLA-C * 07:01g, HLA-DRB1 * 03:01, HLA-DQB1 * 02:01g, and HLA-DRB3 * 01:
01. A cell homozygously having at least one, two, three, four, or all of the group consisting of: 【Request Item 8】 HLA-A * 01:01g, HLA-B * 57:01g, HLA-C * 06:02g, HLA-DRB1 * 07:01, HLA-DQB1 * 03:03g, and HLA-DRB4 * 01:01g. A cell homozygously comprising at least one, two, three, four, or all of the following: 【Request Item 9】 HLA-A * 02:01g, HLA-B * 40:01g, HLA-C * 03:04g, HLA-DRB1 * 13:02, HLA-DQB1 * 06:04g, and HLA-DRB3 * 03:
01. 【Request Item 10】 HLA-A * 24:02g, HLA-B * 07:02g, HLA-C * 07:02g, HLA-DRB1 * 15:01, HLA-DQB1 * 06:02, and HLA-DRB5 * 01:
01. A cell homozygously having at least one, two, three, four, or all of the group consisting of: 【Request Item 11】 HLA-A * 24:02g, HLA-B * 52:01g, HLA-DRB1 * 15:02, HLA-C * 12:02, HLA-DRB5 * 01:02g, and HLA-DQB1 * 06:
01. 【Request Item 12】 HLA-A * 33:03g, HLA-B * 44:03, HLA-DRB1 * 13:02, HLA-C * 14:03, HLA-DRB3 * 03:01, and HLA-DQB1 * 06:04g. 【Request Item 13】 HLA-A * 24:02g, HLA-B * 07:02g, HLA-DRB1 * 01:01, HLA-C * 07:02g, HLA-DRBX * NNNN and HLA-DQB1 * 05:
01. 【Request Item 14】 HLA-A * 24:02g, HLA-B * 54:01g, HLA-DRB1 * 04:05, HLA-C * 01:02g, HLA-DRB4 * 01:01g, and HLA-DQB1 * 04:01g. 【Request Item 15】 HLA-A * 24:02g, HLA-B * 59:01, HLA-DRB1 * 04:05, HLA-C * 01:02g, HLA-DRB4 * 01:01g, and HLA-DQB1 * 04:01g. 【Request Item 16】 HLA-A * 02:07g, HLA-C * 01:02g, HLA-B * 46:01g, HLA-DRBX * NNNN, HLA-DRB1 * 08:03, and HLA-DQB1 * 06:
01. 【Request Item 17】 HLA-A * 11:01g, HLA-C * 04:01g, HLA-B * 15:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:06, and HLA-DQB1 * 03:02g. 【Request Item 18】 HLA-A * 11:01g, HLA-C * 01:02g, HLA-B * 54:01g, HLA-DRB4 * 01:01g, HLA-DRB1 * 04:05, and HLA-DQB1 * 04:01g. 【Request Item 19】 HLA-A * 26:01g, HLA-C * 03:04g, HLA-B * 40:02g, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * 03:03g. 【Request Item 20】 HLA-A * 24:02g, HLA-C * 08:01g, HLA-B * 40:06, HLA-DRB4 * 01:01g, HLA-DRB1 * 09:01, and HLA-DQB1 * 03:03g. 【Request Item 21】 HLA-A * 02:01, HLA-C * 06:02, and HLA-DPA1 * 01:03.
Citation Information
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