FIELD: medicine.
SUBSTANCE: group of inventions relates to stimulation of donor-specific tolerance to an allogenic whole organ transplant obtained from a donor in a recipient in need of whole organ transplantation. Method for stimulating donor-specific tolerance to an allogenic whole organ transplant obtained from a donor in a recipient in need of whole organ transplantation, wherein said whole organ is a heart, kidney, liver, lung, pancreas, small intestine or large intestine, or a combination thereof, wherein the method involves the following steps: (a) removal of thymus from recipient; (b) administering to said recipient an immunosuppression induction regimen comprising one or more immunosuppressive preparations, to deplete T-cells of said recipient and/or to inhibit the ability of T-cells of said recipient to reject the transplanted whole organ; (c) providing both a suitable whole human organ and a thymus from a donor; (d) transplanting a whole human organ into said recipient; (e) administering an immunosuppression regimen to said recipient; (f) providing a product derived from allogenic cultured tissue of postnatal thymus, wherein said product obtained from allogenic cultured tissue of postnatal thymus is obtained by means of: providing suitable thymus tissue of said whole organ donor obtained in step (c), treating thymus tissue of said whole organ donor aseptically to section donor thymus tissue, subjecting said donor thymus tissue sections to a conditioning regimen for up to 21 days by culturing donor thymus tissue in thymus organ medium to obtain partially T-cell-depleted sections of donor thymus tissue; where the donor thymus tissue sections partially depleted of T-cells show between 5th and 9th day of the conditioning regimen a cytokeratin (CK) positive staining area, presence of at least one Hassall's corpuscle and the presence of intact nuclei of thymic epithelial cells and other stromal cells in said partially T-cell-depleted sections of donor thymus tissue; and (g) implanting a product derived from allogenic cultured postnatal thymus tissue into said recipient after 12 to 21 days of the conditioning regimen, wherein the dosage of the partially T-cell depleted sections of thymus tissue is 1,000–20,000 mm2 +/−10% of the surface area of the thymus tissue per recipient body surface area in m2, and further wherein the implanted product obtained from the allogenic cultured tissue of the postnatal thymus induces thymopoiesis and tolerance in said recipient. Use of a product obtained from allogenic cultured tissue of postnatal thymus for implantation in a subject undergoing whole organ transplantation for stimulation of donor-specific tolerance, wherein said whole organ is a heart, kidney, liver, lung, pancreas, small intestine or colon or a combination thereof, and where said product is obtained by: obtaining suitable thymus tissue from a donor, wherein the donor thymus tissue is subjected to a conditioning regimen for a period of up to 21 days; wherein the conditioning regimen for the donor thymus tissue comprises treating the donor thymus tissue in an aseptic manner in a thymus organ medium to obtain partially T-cell-depleted sections of the donor thymus tissue; wherein said partially T-cell depleted sections of donor thymus tissue show, between 5th and 9th day of the conditioning regimen, areas positive for CK staining, presence of at least one Hassall's corpuscle and the presence of intact nuclei of thymic epithelial cells and other stromal cells in said partially T-cell-depleted sections of donor thymus tissue; and extraction of partially depleted T-cells sections of donor thymus tissue as a product obtained from allogenic cultured tissue of postnatal thymus.
EFFECT: method and use described above effectively stimulate donor-specific tolerance to an allogenic whole organ transplant obtained from a donor in a recipient in need of whole organ transplantation, effectively reduces graft rejection in whole organ transplantation, preserves organ viability before and during the implantation procedure.
71 cl, 33 dwg, 9 tbl, 5 ex
Authors
Dates
2024-12-04—Published
2019-02-22—Filed