The present disclosure provides engineered thymic epithelial cells and cell lines, as well as extracellular vesicles derived therefrom. The disclosure also provides exosomes that display specific surface proteins, and provides methods for using said materials for treating subjects and for identifying cells.

Methods and compositions for promoting donor-specific tolerance and immunocompetence to a recipient of a solid organ transplant, by implanting an allogeneic solid organ in a recipient in need of a solid organ transplant and further comprising surgical implantation of a tissue-engineered allogeneic cultured postnatal thymus tissue product in the recipient of a solid organ from a donor. Methods of producing an allogeneic cultured postnatal thymus tissue-derived product suitable for implantation into a human; methods of culturing allogeneic cultured postnatal thymus tissue-derived product suitable for implantation into a human and methods of using allogeneic cultured postnatal thymus tissue-derived product by implantation in a human subject.

Methods and compositions for promoting donor-specific tolerance and immunocompetence to a recipient of a solid organ transplant, by implanting an allogeneic solid organ in a recipient in need of a solid organ transplant and further comprising surgical implantation of a tissue-engineered allogeneic cultured postnatal thymus tissue product in the recipient of a solid organ from a donor. Methods of producing an allogeneic cultured postnatal thymus tissue-derived product suitable for implantation into a human; methods of culturing allogeneic cultured postnatal thymus tissue-derived product suitable for implantation into a human and methods of using allogeneic cultured postnatal thymus tissue-derived product by implantation in a human subject.

The present invention provides a thymic epithelial cell production method, the method including a step for culturing thymic epithelial progenitor cells for a long period of time. The present invention also provides a transplant therapeutic agent that includes thymic epithelial cells produced by the production method according to the present invention. The present invention further provides a T cell production method, the method including a feature of causing thymic epithelial cells produced by the production method according to the present invention to contact hematopoietic stem cells or any cells in the process of differentiation from hematopoietic stem cells to T cells.

The use of a composition, which includes the following compounds: Activin A, BMP4, CHIR99, EGF, FGF 8, FGF 10, IGF1, LY3, Noggin, retinoic acid and Y27, for implementing a differentiation process, preferably in vitro or ex vivo, of an induced pluripotent stem cell or iPSc, into a functional thymic epithelial progenitor or TEP.