Transplanted human thymus slices induce and support T-cell development in mice after cryopreservation

Abstract

Here we show that slices of human thymus tissue that have been frozen and thawed can induce and support T-cell development when transplanted into nude mice. Babies born without a thymus require urgent treatment to reconstitute T-cell immunity. Thymus tissue is removed from infants during cardiac surgery, to allow access to the heart. This discarded thymus tissue can be transplanted into athymic infants to reconstitute T-cell immunity. Slices of thymus tissue are transplanted into the thigh, after a two-three week culture period to deplete thymocytes. This procedure is life-saving, but recipients have low T-cell counts, and may develop autoimmunity. It is not possible to attempt to MHC-match transplants between-donor and recipient because of the urgency of performing the procedure. As delays in thymus transplantation could be life-threatening, the procedure would be improved if it were possible to freeze thymus slices for transplantation. Cryopreservation would also open up the possibility of partial MHC-matching. We adapted a slow cooling protocol based on cryopreservation of ovarian tissue fragments to freeze slices of human thymus of 1mm thickness and showed that on thawing such slices can induce and support T-cell development in vivo in an animal model.

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