Reconstitution of thymopoiesis via implantation of cryopreserved cultured thymus tissue into athymic recipients.

Implantation of cultured allogeneic thymus tissue (CTTI) into athymic human recipients generates functional recipient-derived naïve T cells that are tolerant to the donor. Currently, CTTI is always performed with 12 to 21 days of thymus procurement to avoid culture-related changes that could be detrimental to its reconstitution potential. We demonstrate here that cultured thymus tissue can be cryopreserved and still maintain its viability and reconstitution potential. Implantation of cryopreserved cultured rat thymus tissue (cCTTI) under the renal capsule of congenitally athymic rats results in colonization of the thymus implant with T cell progenitors and population of the periphery with genetically-recipient naïve T cells. Similarly, cCTTI of porcine thymus into the quadriceps muscle of thymectomized T cell-depleted pigs results in full reconstitution of the implanted thymus. Human thymus tissues that are similarly cultured and cryopreserved continue to meet the same implantation quality criteria as freshly cultured thymus tissue. Clinical trials are warranted to test the potential of cCTTI to decouple the current links between time of procurement and implantation. This would extend the benefits of immune reconstitution and tolerance induction to a broader range of patients.