Abstract: Provided herein are recombinant miniature swine without expression of endogenous porcine CD47 and SIRPA, but with the expression of human or humanized CD47 and human or humanized SIRPA under the same regulatory elements as the endogenous porcine CD47 and SIRPA. Also provided are cells, tissues, and organs derived from such recombinant miniature swine. Furthermore, provided herein are methods of transplanting a graft from a first donor of such recombinant miniature swine with or without bone marrow from a second donor of such recombinant miniature swine.

Abstract: Provided herein are methods of xenotransplantation, for example, porcine to human transplantation. Also provided herein are extracellular vesicles (“EVs”, e.g., exosomes) and compositions comprising the same. e.g. EVs expressing human CD47. Further provided herein are methods of making EVs and use thereof for xenotransplantation. In some aspects, the methods of xenotransplantation comprise steps of expressing human CD47 on xenografts.

Abstract: CAR Tregs and Tregs are provided which are both conversion-resistant and condition-resistant. The Treg cells are engineered such that they are deficient in or substantially devoid of a cell-surface marker or antigen.

Abstract: Described herein are methods of cell therapies. Also described herein are methods of establishing a mixed chimerism, and/or preventing a rejection of a donor organ in a subject wherein said subject has received an organ transplant, the method comprising administering to said subject a population of hematopoietic cells, wherein said organ transplant comprises a heart transplant.

Abstract: Described herein are methods of cell therapies. Also described herein are methods of generating donor derived T cells in an organ transplant recipient, by administering bone marrow stem cells to the organ transplant recipient about 1 to about 30 days after the organ transplant recipient receives one or more organ transplants.

Abstract: Provided herein are recombinant miniature swine expressing human CD47 in a tissue specific fashion. Also provided are kidneys isolated from a miniature swine, wherein the glomeruli of the kidney express human CD47 at a level higher than the level of human CD47 expression in the tubules of the kidney. Furthermore, provided herein are methods of transplanting such swine kidneys with glomeruli-specific expression of human CD47 from recombinant miniature swine into human recipients. In certain aspects, provided herein are methods of transplantation comprising transplanting hematopoietic stem cells expressing human CD47 from a first donor animal (e.g., a miniature swine) and a kidney expressing human CD47 in the glomeruli from a second donor animal (e g., a miniature swine) to a recipient (e.g., a human recipient).

Abstract: Described herein are methods of cell therapies. Also described herein are methods of generating donor derived T cells in an organ transplant recipient, by administering bone marrow stem cells to the organ transplant recipient about 1 to about 30 days after the organ transplant recipient receives one or more organ transplants.

Abstract: The present disclosure provides for transgenic swine, comprising one or more nucleotide sequences encoding one or more HLA I polypeptides and/or one or more HLA II polypeptides inserted into one or more native SLA loci of the swine genome, methods of making and methods of using. The present disclosure also provides for improved methods of making human immune system mice.

Abstract: Described herein are methods of cell therapies. Also described herein are methods of generating donor derived T cells in an organ transplant recipient, by administering bone marrow stem cells to the organ transplant recipient about 1 to about 30 days after the organ transplant recipient receives one or more organ transplants.

Abstract: The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Abstract: The current disclosure provides for methods of promoting differentiation of pluripotent stem cells into thymic epithelial cells or thymic epithelial cell progenitors as well as the cells obtained from the methods, and solutions, compositions, and pharmaceutical compositions comprising such cells. The current disclosure also provides for methods of using the thymic epithelial cells or thymic epithelial cell progenitors for treatment and prevention of disease, generating organs, as well as other uses, and kits.

Abstract: The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Abstract: The present disclosure provides for conversion-resistant CAR regulatory T cells (Tregs) and bi-specific antibodies, and methods to use these Tregs and antibodies for the treatment of autoimmune diseases and for prevention of organ transplant rejection.

Abstract: The present disclosure relates to making a hybrid pig-human thymic tissue and using the hybrid thymic tissue to induce tolerance in xenotransplantation. The hybrid thymic tissue can also be used for restoring or inducing immunocompetence in a recipient as well as restoring or promoting thymus-dependent ability for T cell progenitors to develop into mature functional T cells in a recipient.

Abstract: The present disclosure provides for methods to produce B cell-expanded Tregs that are more stable and more effective than donor-specific Tregs for suppressing polyclonally activated T cells. In certain embodiments, the present polyclonal Tregs can react to many donors, not just a specific donor.

Abstract: The invention provides an animal model and methods of generating large numbers of diverse, functional, naïve T cells in mice using bone marrow cells from adult donors.

Abstract: The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Abstract: The invention provides for the use of deep sequencing of the T-cell receptor beta CDR3 to identify, then track donor specific and/or recipient specific T cells in blood, urine and/or end-organs of transplant recipients.

Abstract: Methods and compositions for modulating immune responses are provided herein.

Abstract: The invention provides an animal model and methods of generating large numbers of diverse, functional, naïve T cells in mice using bone marrow cells from adult donors.