65 results about "Induced pluripotent stem cell" patented technology

Disclosed in the present invention are a biomimetic vascularized iPSC-hep spheroid for liver regeneration, and a preparation method therefor. The biomimetic vascularized iPSC-hep spheroid is a microcapsule with a porous hyaluronic acid methacryloyl as a shell and a human-induced pluripotent stem-cell-derived hepatocyte spheroid as an inner phase, and human umbilical vein endothelial cells adhere to the surface of the shell. The biomimetic vascularized iPSC-hep spheroid of the present invention promotes effective communication between hiPSC-heps and HUVECs, and provides barrier protection for an encapsulated hiPSC-hep spheroid so as to avoid attack by the immune system. Compared with dispersed cells, the cell-to-cell interaction in the cell spheroid improves cell-to-cell communication, helps to simulate the physiological heterogeneous structure and cell microenvironment of the liver, and can more effectively repair an acutely failing liver.

According to one embodiment, an initialization agent is for initializing blood cells derived from peripheral blood. The initialization agent includes an initialization factor group for producing iPS cells by initializing a group of blood cells including mononuclear cells derived from peripheral blood, and a group of lipid nanoparticles that encapsulate the initialization factor group. The lipid nanoparticles have a component of at least or more of 40% FFT-10 and FFT-20. FFT-10 and FFT-20 are included in equal amounts.

Provided are a method for inducing differentiation of pluripotent stem cells into CD34+ hematopoietic stem / progenitor cells and a culture medium composition thereof. Provided are a method for inducing differentiation of pluripotent stem cells into CD34+ hematopoietic stem / progenitor cells or NK cells and a culture medium composition thereof. The NK cells obtained using the provided culture method have high purity and good in vitro expansion effect; the yield of iNK cells is high, and a single iPSC can differentiate into approximately 2,000 NK cells; and the obtained iNK cells highly express CD16 (over 70%). As a result, the problem of low CD16 expression in iNK cells in the prior art, which requires genetic modification methods to solve, has been addressed.

Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

The present invention relates to a method for producing adipocyte-derived dedifferentiated stem cells by using centrifugation. The method for producing adipose cell-derived dedifferentiated stem cells by using centrifugation, and adipose cell-derived dedifferentiated stem cells using same, according to one embodiment of the present invention, allow a production period to be significantly shorter than that of adipose cell-derived dedifferentiated stem cells produced using a conventional ceiling culture method, and thus can be effectively used in the field of autologous adipose-derived stem cell therapeutic agents.

A method of assessing the safety of a gene therapy vector comprising: providing a population of genetically modified cells 18 wherein the cells have been transfected with a vector; exposing the genetically edited cells to a carcinogen 20; growing the cells to produce immortal cell lines; and comparing the survival of the test cells with a control 14 to determine if the vector contributes to carcinogenicity. Also claimed is a method of testing the safety of a vector comprising: providing test cells; genetically editing the cells with a vector and exposing cells to a carcinogen or exposing the cells to a carcinogen and modifying the cells with a vector; growing the cells; and comparing the survival of the cells to a control. The cells may be used in immunotherapy. The cells may be CAR-T cells. The cells may be from peripheral blood mononuclear cells or induced pluripotent stem cells (iPSCs). The carcinogen may be ENUA. Also claimed is a method of designing a vector for use in gene therapy by harvesting nucleic acid from the test cells, characterising the modification of the test cells, redesigning the vector, and repeating the method of testing the safety of the vector.

The present disclosure relates to genetically modified cells (e.g., iPSC, IPS-derived immune cells, e.g., NK or T cells, or NK cells or T cells) comprising a disrupted FAS gene, an insertion of a polynucleotide encoding an IL15 / IL15Rα fusion, and an insertion of a polynucleotide encoding a CAR, e.g., an anti-GPR87 CAR. Therapeutic uses of the genetically modified cells to treat cancer (e.g., a lung cancer) are also provided.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

[Summary] [Problems] The main purpose of this invention is to provide a technique for inducing an epidermal keratinocyte that can produce a three-dimensional cultured skin model with a multi-layered horny cell layer, from a pluripotent stem cell. [Solution] The present invention is a method for inducing differentiation from a pluripotent stem cell to an epidermal keratinocyte, using a non-detached cell after being treated with a cell detaching agent in the inducing step from the pluripotent stem cell, wherein when applying the epidermal keratinocyte to a three-dimensional cultured skin model, a three-dimensional cultured skin model in which the horny cell layer is multi-layered is obtained.

The present invention provides: a method for differentiating pluripotent stem cells into mesenchymal stem cells in the presence of a BMP4 signaling agonist; mesenchymal stem cells obtained thereby; and extracellular vesicles obtained from a culture solution of the stem cells. The extracellular vesicles have excellent anti-inflammatory effects, and thus can be used for treating inflammatory diseases. Therefore, there is a high possibility that a composition comprising the extracellular vesicles can be variously used as a pharmaceutical composition for treatment of inflammatory diseases and a cosmetic composition for skin improvement.

Disclosed are methods for culturing coronavirus particles in early syncytiotrophoblasts (eSTBs). The derived eSTBs are mononucleated or bi-nucleated cells with high ACE2 expression and are not multi-n

Provided are a pharmaceutical composition or a pharmaceutical composition raw material, which contains supernatant from a culture medium used during culture to induce pluripotent stem cells.

The present invention relates to a pharmaceutical composition for the prevention or treatment of epilepsy, and an epilepsy therapeutic agent screening method and a composition therefor, and specifically provides an epilepsy therapeutic agent screening method and an epilepsy therapeutic agent screening composition using induced pluripotent stem cells (iPSCs) derived from an epilepsy patient having a genotype comprising an SCN2A gene mutation, and accordingly, a pharmaceutical composition for the prevention or treatment of epilepsy having more excellent efficacy and selectivity than conventional epilepsy therapeutic agents may be screened and provided.

The invention provides a preparation method of adult T cells and universal adult CAR-T cells induced and differentiated by pluripotent stem cells, and belongs to the technical field of cell differentiation. By intervening the SP140 gene or SP140 protein, advanced hematopoiesis of pluripotent stem cells can be induced, and hematopoietic precursor cells and adult T cells with T gonadotrophy differentiation potential are obtained. The inducible CAR is knocked into the TRAC site of the pluripotent stem cell at a fixed point, so that endogenous regulation of CAR expression is realized, the in-vivo maintenance and anti-tumor capability of CAR-T is improved, and TCR-mediated graft versus host disease is blocked. The invention also provides a separated CAR-T cell, the CAR-T cell aiming at different antigens can be prepared by editing a seed cell of a pluripotent stem cell once, B2M and CIITA genes are further knocked out, HLA-E is overexpressed, and the immunogenicity of the CAR-T cell and the resistance of a host to the CAR-T cell are reduced.

The present invention relates to NK cells with an improved ability to target and kill cancer cells and use thereof. Specifically, the present invention relates to: iPSC-based NK cells into which a chimeric antigen receptor targeting a specific cancer antigen, CXCR4 and CCR7 genes, which are chemokine receptors, and an IL-15 / IL-15Rα (IL-15RF) gene are introduced; and use thereof for treating cancer. The iPSC-based NK cells according to the present invention can not only directly target a specific cancer antigen by the introduced CAR, but can also activate NK cells and enhance the proliferation thereof by regulating intracellular signaling and tumor microenvironment by the introduced CXCR4 and CCR7 and the introduced IL-15RF. Therefore, the NK cells into which multiple genes are introduced, according to the present invention, can efficiently target and attack cancer cells, and thus can be effectively used for the treatment of cancer diseases.

Provided are a cold storage method and a cold storage liquid that are suitable for non-freezing refrigerated storage of human or animal stem cells such as iPS cells or embryos in a non-frozen state. According to an embodiment, the non-freezing refrigerated storage liquid is: a mixture liquid (HTMα, HTMx2c13), in which MEM-alpha (Minimum Essential Medium Eagle (MEM) Alpha Modification) is mixed with a UW solution (UW_sln; BELZER UW (registered trademark) COLD STORAGE SOLUTION), or a modified UW solution (polymer component being changed to PVA), are mixed in a ratio of about 1 / 1 to 1 / 2; or a storage liquid having a composition equivalent to the mixture liquid, especially in respect of concentrations of potassium ions and sodium ions. And, arousal period(s) of maintaining a temperature of 30° C. to 37° C. is inserted at each of two to five days, into a non-freezing refrigerated storage period, which is made at 2° C. to 8° C. for 2 to 10 days or 4 to 20 days.

Described herein are methods and culture medium, useful for inducing polarization in multipotent stem cells. Additionally, described herein are multipotent cells produced by the methods and culture medium of this disclosure that are useful therapeutic agents. Also described herein are extracellular vesicles and factors secreted by multipotent cells that are produced by the methods and culture medium of this disclosure that are useful as therapeutic agents.

The invention discloses a kit and a method for constructing a human bone organoid from pluripotent stem cells, and relates to the technical field of organoid culture. The kit for constructing the human bone organoid by the pluripotent stem cells comprises a culture medium A, a culture medium B, a culture medium C, a culture medium D and a culture medium E. The culture medium A induces the pluripotent stem cells to form original stripes, the culture medium B induces the original stripes to form paraaxial mesoderm, the culture medium C induces the paraaxial mesoderm to form body wall mesoderm, the culture medium D induces body wall mesoderm cells to differentiate to bone cells, and the culture medium E induces bone cells to form cartilage organs. The kit provided by the invention can induce the pluripotent stem cells into bone organs, and has important significance in research and treatment of pathogenesis of bone related diseases and related research of bone repair and regeneration.

A composition for preventing or treating cancer or infectious disease is disclosed. The composition contains, as an active ingredient, a pluripotent stem cell-derived immune cell expressing IL-7, CCL19, or a combination thereof. The composition provides a multifaceted and synergistic therapeutic effect derived from the complementary immune response of the patient's endogenous T cells and the injected natural killer cells, by administering only a therapeutically effective amount of immune cells other than T cells, specifically natural killer cells. The natural killer cells of the composition may also be co-administered with exogenous T cells to allow these different cell populations to act more intensively at the lesion site. The composition is based on the differentiation of pluripotent stem cells, specifically induced pluripotent stem cells (iPSCs) into immune cells, thus can be used to generate an unlimited supply of allogenic or autologous cells as needed.

To provide a technology for homogeneously producing induced pluripotent stem cells.SOLUTION: According to one embodiment, an initialization agent for initializing blood cells derived from peripheral blood includes an initialization factor group for producing iPS cells by initializing a group of blood cells including mononuclear cells derived from peripheral blood, and a group of lipid nanoparticles that encapsulate the initialization factor group. At least 40% of the components of the lipid nanoparticles are FFT-10 and FFT-20. FFT-10 and FFT-20 are included in equal amounts.SELECTED DRAWING: Figure 1

The present disclosure relates to methods and compositions for reprogramming cells to a pluripotent state. In particular, it relates to an integration- and feeder cell-free method for reprogramming primary human fibroblast cells to induced pluripotent stem cells (iPSCs).

The invention belongs to the technical field of stem cell induction, and discloses an epigenetic regulation-based iPSC (induced pluripotent stem cell) efficient directional induction method, which is characterized in that 5-azacytidine, vitamin C and alpha-ketoglutaric acid are added into somatic cells before induction so as to regulate DNA (deoxyribonucleic acid) methylation level and histone modification state, relieve an epigenetic inhibition structure and activate a pluripotent gene promoter region. Then, under the condition of no virus and no integrated vector, two specific micromolecules RG108 and MGCD0103 are introduced to respectively target DNA methyltransferase and histone deacetylase, and are matched with vitamin C to enhance TET enzyme activity, so that the somatic cells are efficiently induced to be reprogrammed into the induced pluripotent stem cells. The obtained iPSC has high clone formation rate, typical pluripotent marker expression and good genetic stability, has the advantages of high safety, high efficiency and short period, and is suitable for clinical research and individualized regenerative medicine application.

Disclosed are methods for making a vascularized hollow organ derived from human intestinal organoid (HIOs). The HIOs may be obtained from human embryonic stem cells (ESC's) and / or induced pluripotent stem cells (iPSCs), such that the HIO forms mature intestinal tissue. Also disclosed are methods for making a human intestinal tissue containing a functional enteric nervous system (ENS).

The present invention provides: a method for differentiating pluripotent stem cells into mesenchymal stem cells in the presence of a BMP4 signaling agonist; mesenchymal stem cells obtained thereby; and extracellular vesicles obtained from a culture solution of the stem cells. The extracellular vesicles have excellent anti-inflammatory effects, and thus can be used for treating inflammatory diseases. Therefore, there is a high possibility that a composition comprising the extracellular vesicles can be variously used as a pharmaceutical composition for treatment of inflammatory diseases and a cosmetic composition for skin improvement.

Provided are a pharmaceutical composition or a pharmaceutical composition raw material, which contains supernatant from a culture medium used during culture to induce pluripotent stem cells.

The present application provides a method for producing, from pluripotent stem cells, neural progenitor cells of the midbrain floor plate region or dopaminergic neural progenitor cells, the method comprising (1) inducing differentiation of pluripotent stem cells into neural progenitor cells of the midbrain floor plate region, and optionally (2) inducing differentiation of the neural progenitor cells of the midbrain floor plate region, which are obtained by the differentiation induced in (1), into dopaminergic neural progenitor cells, wherein all or part of the differentiation induced in (1) includes culturing the cells in a medium containing an agonist for LPA receptor.

In particular, compositions comprising iPSC-derived parietal cell precursors (iMPCs) generated using NK3 homeobox 1 (NKX3.1; parietal cell fate-determining transcription factor) and methods for their preparation and use are described herein. In addition, in particular, methods for maturing iMPCs into functional parietal cell subtypes, including smooth muscle cells, perivascular cells, and fibroblasts, as well as methods for increasing angiogenesis, angiogenesis, and cell junctions, are described herein. iMPCs mediate the formation of functional blood vessels when transplanted together with endothelial cells (ECs); thus, methods for modeling vascular diseases (e.g., 3D vascular organoids (VOs)) and therapeutic vascularization, comprising a method of administering iMPCs and ECs and a step of administering iMPCs and ECs, are also described herein.

This invention provides a gene therapy for Deutsche Syndrome (DSS) and relates to the field of clinical medical technology. It provides highly efficient pegRNA / ngRNA sequences and their application methods, validating the effectiveness of the lead editing system in treating SDS in two in vitro models: induced pluripotent stem cells (iPSCs) and hematopoietic stem / progenitor cells (HSPCs). Furthermore, the therapeutic effect of lead editing on SDS was identified in vivo by transplanting edited HSPCs, laying the foundation for clinical translation.

The present invention provides a method for producing an artificial bone-cartilage complex, the method comprising: (i) a step for inducing differentiation of pluripotent stem cells to obtain a precartilage cell mass; (ii) a step for seeding and culturing the precartilage cell mass obtained in the step (i) on the surface of an artificial bone having communication holes; and (iii) a step for recovering an artificial bone-cartilage complex in which a cartilage layer is formed on the surface of the artificial bone. Also provided is an artificial bone-cartilage complex produced by said method.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing a chimeric antigen receptor (CAR) and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.