32 results about "Allogeneic transplantation" patented technology

The present invention relates to the use of umbilical cord blood cells from a donor or patient to provide neural cells which may be used in transplantation. The isolated cells according to the present invention may be used to effect autologous and allogeneic transplantation and repair of neural tissue, in particular, tissue of the brain and spinal cord and to treat neurodegenerative diseases of the brain and spinal cord.

A method of isolating epithelial cells from a human skin tissue or internal organ tissue using trypsin and ethylenediamine tetraacetic acid (EDTA) simultaneously with the application of magnetic stirring, a method of preconditioning isolated biological cells by the application of physical stimulus, i.e., strain, are provided. Epithelial cells can be isolated by the method with increased yield, colony forming efficiency (CFE), and colony size. Also, the increased percentage of stem cells in isolated cells is advantageous in therapeutic tissue implantation by autologous or allogeneic transplantation. In skin cells preconditioned by the application of strain, cell division is facilitated, and the secretion of extracellular matrix components and growth factors and the activity of matrix metalloproteinases (MMPs) are improved. When preconditioned cells are implanted by autologous or allogeneic transplantation to heal a damaged tissue, the improved cell adhesion, mobility, and viability provides a biological adjustment effect against a variety of stresses or physical stimuli which the cells would undergo after implantation, with improved capability of integration into host tissue, thereby markedly improving the probability of success in skin grafting.

The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and / or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and / or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and / or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.

The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) comprising (1) measuring the expression level of human leukemic stem cell (LSC) marker genes in a biological sample collected from a subject for a transcription product or translation product of the gene as an analyte and (2) comparing the expression level with a reference value; an LSC-targeting therapeutic agent for AML capable of suppressing the expression of a gene selected from among LSC marker genes or a substance capable of suppressing the activity of a translation product of the gene; a method for producing a sample containing hematopoietic cells for autologous transplantation or allogeneic transplantation for AML patients comprising obtaining an LSC-purged sample with at least 1 kind of LSC marker as an index; and a method of preventing or treating AML.

The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and / or class I I major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and / or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and / or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.

A method of isolating epithelial cells from a human skin tissue or internal organ tissue using trypsin and ethylene-diamine tetraacetic acid (EDTA) simultaneously with the application of magnetic stirring, a method of preconditioning isolated biological cells by the application of physical stimulus, i.e., strain, are provided. Epithelial cells can be isolated by the method with increased yield, colony forming efficiency (CFE), and colony size. Also, the increased percentage of stem cells in isolated cells is advantageous in therapeutic tissue implantation by autologous or allogeneic transplantation. In skin cells preconditioned by the application of strain, cell division is facilitated, and the secretion of extracellular matrix components and growth factors and the activity of matrix metalloproteinases (MMPs) are improved. When preconditioned cells are implanted by autologous or allogeneic transplantation to heal a damaged tissue, the improved cell adhesion, mobility, and viability provides a biological adjustment effect against a variety of stresses or physical stimuli which the cells would undergo after implantation, with improved capability of integration into host tissue, thereby markedly improving the probability of success in skin grafting.

Provided is a technology involving differentiating preadipocytes, derived from human adipose tissues, into adipocytes and transplanting the differentiated adipocytes in conjunction with a biodegradable scaffold into the body. According to the present invention, when immature adipocytes having a cell diameter of 20 to 40 μm, obtained by differentiation of adipose tissue-derived preadipocytes into adipose tissues, are used in conjunction with a scaffold in autologous or allogeneic transplantation, maturation of adipocytes at the target transplantation site leads to a gradual increase in the volume of adipocytes. Therefore, the adipocyte-scaffold composition according to the present invention can be utilized as an effective body volume replacement and can treat various disorders due to defects of soft tissues or aesthetic defects in appearance.

The present invention pertains to engineered immortalized T-cell lines, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immortalized T-cell lines of the invention are characterized in that the expression of endogenous T-cell receptors (TCRs) and beta 2-microglobulin (B2M) is inhibited, e.g., by using an endonuclease able to selectively inactivate the TCR and B2M genes in order to render the immortalized T-cells non-alloreactive. In addition, expression of immunosuppressive polypeptide can be performed on those engineered immortalized T-cells in order to prolong the survival of these T-cells in host organisms. Such engineered immortalized T-cells are particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immortalized T-cells for treating cancer, infections and auto-immune diseases.

A method of treating or preventing an immune disorder, such as graft versus host disease, in a subject. The method includes the administering a SHIP1 inhibitor, such as 3α-aminocholestane, to a subject in need of treatment. Thus, SHIP1 inhibitors taught herein represent a novel class of small molecules that have the potential to enhance allogeneic transplantation, boost innate immunity and improve the treatment of hematologic malignancies.

The present invention relates to the use of umbilical cord blood cells from a donor or patient to provide neural cells which may be used in transplantation. The isolated cells according to the present invention may be used to effect autologous and allogeneic transplantation and repair of neural tissue, in particular, tissue of the brain and spinal cord and to treat neurodegenerative diseases of the brain and spinal cord.

The present invention relates, generally, to methods and compositions for allogeneic transplantation. More particularly, the invention relates to the use of alloreactive natural killer cells in order to enhance the efficacy and / or safety of allogeneic grafts in human subjects. The invention allows to increase the engraftment of an allogeneic grafts, even in myelo-reductive conditioning, to protect against GVHD and / or to eradicate malignant cells. The invention is particularly suited in allogeneic hematopoietic transplantations, particularly bone marrow transplantations.

It is intended to provide anticancer therapy using autologous cells or the like, which induces the regression of cancer or has favorable drug delivery effects and brings about reduction or withdrawal of a hypoxic region(s) in tumor. Transplantation of endothelial progenitor cells, via intravenously or other methods leads to tumor growth inhibition, an increase of the vascular density with an enlargement of the vascular diameter, and reduction of a hypoxic region(s) in the tumor. Allogeneic transplantation of endothelial progenitor cells may be achieved to secure the cells for the therapy, however, autologous transplantation of endothelial progenitor cells from cancer patients would be desirable in order to evade rejection. When the autologous cells are used, mononuclear cells are separated from the peripheral blood or bone marrow of the patient and cultured using an endothelial differentiation medium containing cytokines such as VEGF to obtain adherent cells, which can then be collected and advantageously used as endothelial progenitor cells.

The present invention pertains to engineered immortalized T-cell lines, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immortalized T-cell lines of the invention are characterized in that the expression of endogenous T-cell receptors (TCRs) and beta 2-microglobulin (B2M) is inhibited, e.g., by using an endonuclease able to selectively inactivate the TCR and B2M genes in order to render the immortalized T-cells non-alloreactive. In addition, expression of immunosuppressive polypeptide can be performed on those engineered immortalized T-cells in order to prolong the survival of these T-cells in host organisms. Such engineered immortalized T-cells are particularly suitable for allogeneic transplantations, especially because it reducesboth the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immortalized T-cells for treating cancer, infections and auto-immune diseases.

The present invention relates to a compound of formula (I), a stereomeride, pharmaceutically acceptable salt, a solvate or an N-oxide thereof, a medicine composition comprising the compound, a method for preparing the compound, and a usage of the compound in treating diseases related to Hsp70. The diseases are preferably selected from tumors, neurodegenerative diseases, and allogeneic transplantation rejection and infection.

The stem cells that can be propagated and maintained for extended periods of time in culture in the absence of a feeder layer, and can be used to repair tissue damage. These cells are derived from fetal tissues and are able to repair different types of damage in musculoskeletal system, with significantly greater efficacy than stem cells derived from adult tissues. These cells are hypoimmunogenic and can be used for allogeneic transplantation to vertebrate hosts having disease and / or damage in musculoskeletal and other tissues. The cells can be administered by direct injection to the site in need of repair or by systemic (e.g., intravenous) administration. The stem cells of the invention are capable of migrating to the sites in need of repair, and of adopting a phenotype most appropriate to the nature of the damage, injury or disease.

The present invention pertains to engineered immortalized T-cell lines, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immortalized T-cell lines of the invention are characterized in that the expression of endogenous T-cell receptors (TCRs) and beta 2-microglobulin (B2M) is inhibited, e.g., by using an endonuclease able to selectively inactivate the TCR and B2M genes in order to render the immortalized T-cells non-alloreactive. In addition, expression of immunosuppressive polypeptide can be per-formed on those engineered immortalized T-cells in order to prolong the survival of these T-cells in host organisms Such engineered immortalized T-cells are particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the hosts immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immortalized T-cells for treating cancer, infections and auto-immune diseases.

The invention discloses a method for screening a new subset of periodontal ligament specific stem cells based on single cell sequencing and application thereof. The screened new subset specifically expresses FBLN2 and membrane protein CADM3, and meanwhile, the invention discloses application of the new subset of periodontal ligament specific stem cells in preparation of drugs for treating periodontal diseases. According to the invention, the subset of periodontal ligament specific stem cells is obtained through single cell sequencing, and in vitro flow sorting and cell subset performance verification are carried out through marker genes; According to the invention, the screened cell subset is beneficial to search for intervention targets of periodontal steady-state imbalance, and creates possibility for development of new drugs; periodontal ligament specific stem cells are used as seed cells to form organoids, and a scientific basis is provided for research and verification of new medical instrument materials; and the autologous / allogeneic transplantation feasibility of the periodontal ligament stem cells is further explored, and a new remodeling thought is provided for treating periodontal diseases.

The invention discloses a method for differentiating and preserving non-integrated feeder-layer-free human urine-derived induced pluripotent stem cells into neural stem cells, and belongs to the technical field of neuroscience and cell biology. The method comprises the following steps of: selecting and collecting urine-derived cells, culturing and amplifying, inducing pluripotent stem cells iPSCsfor induction culture, inducing the pluripotent stem cells to induce differentiation of neural stem cells NSCs, and preserving. According to the method disclosed by the invention, urine is selected asan iPSCs cell source, and the method has the advantages of being easily available, simple, low in cost, non-invasive and the like. The iPSCs cells are induced into NSCs by adopting an episome induction method, the whole link is free of animal-derived cells and other components, feeder layers are avoided, the method is non-integrated and virus infection-free, the availability and safety of the iPSCs-derived neural stem cells are greatly improved, and a novel method is provided for clinical autologous or allogeneic transplantation. Meanwhile, the cultured NSCs are stored in a form of nerve balls and can be preserved for a week at an ambient temperature, and a novel method is provided for long-term preservation and long-distance transportation.

An anticancer therapy using autologous cells or the like, which induces the regression of cancer or has favorable drug delivery effects and brings about reduction or withdrawal of a hypoxic region(s) in tumor is provided. Transplantation of endothelial progenitor cells, via intravenously or other methods leads to tumor growth inhibition, an increase of the vascular density with an enlargement of the vascular diameter, and reduction of a hypoxic region(s) in the tumor. Allogeneic transplantation of endothelial progenitor cells may be achieved to secure the cells for the therapy, however, autologous transplantation of endothelial progenitor cells from cancer patients would be desirable to evade rejection. When autologous cells are used, mononuclear cells are separated from the peripheral blood or bone marrow of the patient and cultured using an endothelial differentiation medium containing cytokines such as VEGF to obtain adherent cells, which can then be collected and used as endothelial progenitor cells.

The invention discloses a method for reprogramming fibroblasts into Sertoli cells in vitro and its application. The method comprises the following steps: introducing into the fibroblasts a fluorescent protein reporter system specifically expressed in Sertoli cells; then introducing substances that improve the expression level and / or activity of the NR5A1 protein; adding G418, culturing for 3-7 days; discarding the liquid phase , add the medium for culturing fibroblasts, and continue culturing for 3‑7d; separate Sertoli cells from the culture system. Experiments have proved that the cells prepared by the above method have completely obtained the characteristics of Sertoli cells, such as attracting endothelial cells, forming lipid droplets, interacting with germ cells, inhibiting the growth of lymphocytes and interleukin production, and immune immunity. . The invention has important application value in the fields of infertility treatment, allogeneic transplantation, cell therapy and the like.

The present invention proposes a method for directly preparing acellular hypertrophic cartilage matrix from adipose tissue, which includes: (1) after in vitro proliferation and culture of particulate adipose tissue, adipose-rich mesenchymal stem cells (ASC) are formed and still have multiple (2) Construction of hypertrophic cartilage tissue in vitro; (3) Preparation of decellularized hypertrophic cartilage matrix. The in vitro endochondral osteogenic induction culture includes two stages of chondrogenic induction culture and hypertrophy induction culture; firstly use chondrogenic induction medium to induce culture, and then use hypertrophy induction medium to induce culture; the above hypertrophic cartilage tissue is decellularized, namely Acellular hypertrophic cartilage matrix was obtained. The immunogenicity of the decellularized hypertrophic cartilage matrix prepared by the invention is greatly reduced, and can be used for allogeneic transplantation.

The invention provides a universal human-derived stem cell suitable for allograft and a construction method thereof. By knocking down or silencing an enhancer gene sequence part of a B2M gene in the stem cell, the stem cell can maintain low immunogenicity in an inflammatory environment and desensitize inflammatory factor IFN-gamma stimulation; and the immune response of allogeneic peripheral blood mononuclear cells is not caused, and meanwhile, the killing effect of allogeneic CD8+T cells and NK cells can be avoided. It is expected that under the condition that HLA matching is not considered, the stem cell can be transplanted into the body of a patient and can be prevented from being attacked by an immune system of the patient, the treatment effect is achieved, and the problem of immunological rejection of the human immune system to allogeneic source cells in a regeneration therapy based on stem cell transplantation is solved.

Disclosed is a method for prediction of an immune response against human leukocyte antigens (HLA) after transplantation, said method comprising HLA-typing of the donor and / or donor material and recipient to determine HLA-mismatches and determination of the number of predicted indirectly recognized HLA epitopes (PIRCHES). In particular, methods for selecting and / or screening donor material for allogeneic transplantation, for example for selecting donor material with permissible mismatches from mismatched unrelated donors and pre-transplantation prediction of an unwanted alloreactivity that could occur after transplantation of hematopoietic stem cells, cord blood, kidneys and / or other cells, tissues or organs are disclosed.

The invention discloses an application of hypodermin A in preparation of a preparation for inhibiting immunological rejection in organ transplantation. According to the invention, an HA transgenetic mouse is prepared and the survival rate of the skin of the HA transgenetic mouse is remarkably higher than that of the skin of a mild mouse by virtue of allogeneic transplantation of the skin of the mouse. The preparation disclosed by the invention can be used for inhibiting immunological rejection in organ transplantation and improving the survival rate of organ transplantation, thereby providing an effective method for treating chronic end-stage diseases of organs such as liver, kidney, heart and the like.

The invention discloses an extension knee apparatus allogeneic transplantation animal model and an establishment method thereof. A New Zealand white rabbit is used as a test object, and the establishment method of the model comprises the following steps: S1, preparation of a graft: taking down a whole extension knee apparatus under a sterile condition, and performing sterile and ultralow-temperature cryopreservation; s2, allogeneic transplantation of the extension knee apparatus: (1) anesthesia, unhairing, disinfection and sheet laying of an allogeneic transplantation object; (2) cutting the middle of the knee joint, longitudinally cutting the whole extension knee apparatus, removing patella and tibial tubercle to form bone grooves, and penetrating a steel wire into the bottom; (3) unfreezing a graft, suturing a quadriceps femoris tendon by using a Krackow method, binding and fixing the tibia in a tibia groove by using a steel wire, and knotting after a suture of the quadriceps femoristendon penetrates out of the quadriceps femoris muscle; and (4) sequentially suturing, straightening and fixing with gypsum. According to the animal model, animal experiments prove that allogeneic transplantation of the extension knee apparatus is a feasible treatment method for incomplete functions of the extension knee apparatus for the first time, and an important experimental basis is provided for clinical development of allogenic transplantation of the human extension knee apparatus.

The invention discloses an application of hypodermin A in preparation of a preparation for inhibiting immunological rejection in organ transplantation. According to the invention, an HA transgenetic mouse is prepared and the survival rate of the skin of the HA transgenetic mouse is remarkably higher than that of the skin of a mild mouse by virtue of allogeneic transplantation of the skin of the mouse. The preparation disclosed by the invention can be used for inhibiting immunological rejection in organ transplantation and improving the survival rate of organ transplantation, thereby providing an effective method for treating chronic end-stage diseases of organs such as liver, kidney, heart and the like.

The present invention relates to a compound of formula (I), a stereomeride, pharmaceutically acceptable salt, a solvate or an N-oxide thereof, a medicine composition comprising the compound, a method for preparing the compound, and a usage of the compound in treating diseases related to Hsp70. The diseases are preferably selected from tumors, neurodegenerative diseases, and allogeneic transplantation rejection and infection.

The invention belongs to the technical field of biomedical engineering, and specifically relates to application and a method of inducing immune rejection in tumor treatment. The inducing immune rejection is the immune rejection induced by transplantation of allogeneic immune cells. The method for tumor treatment by inducing immune rejection specifically comprises sorting CD4+ T cells and injectingCD4+ cells. The immune rejection therapy provided by the present invention skillfully utilizes the immune rejection of body to realize the therapeutic effect on tumors, and a new method is provided for tumor treatment. The preparation of the cells required by the invention is simple, in vitro amplification culture is not needed to carry out, and allogeneic transplantation of exogenous cells can basically cause a recipient to produce immune rejection, so that the treatment has high effective rate and universality.