Background: Mixed chimerism (MC) has been shown to induce tolerance to allogeneic organs and has shown promise for application to xenotransplants, although long-term tolerance has yet to be achieved in primates. We report here the effect on MC and donor skin graft survival of administering host Tregs plus Gal-KO/hCD46/hCD47 transgenic donor pig hematopoietic stem cells (HSC) to baboons.

Methods: Ex-vivo expanded polyclonal host Tregs were grown from sorted (CD4+CD25hi) PBMC and cryopreserved. Mobilized transgenic pig HSC were collected from a Gal-KO/hCD46/hCD47 pig. Four P. hamadryas baboons were conditioned with the protocol and received Tregs and pig HSC. Donor pig skin transplant was performed on day 90 without immunosuppression.

Results: Transient peripheral blood macrochimerism was seen for 1-2 days post PBPC infusions in 3 animals receiving Tregs and for <1 day in a control animal receiving PBSC alone. Skin grafts, completed so far on the first of the experimental animals, showed good vascularization and normal appearance after grafting for over 40 days (Figure 2), at which time a macular rash appeared. Mononuclear cell infiltrates were seen on histology and by day 61 de-epithelialization of the grafts occurred. Mixed lymphocyte reactions showed generalized hyporesponsiveness up to day 149 (day 58 post skin grafting).

Conclusions: Administration of Gal-KO/hCD46/hCD47 pig HSC to baboons, in combination with autologous baboon ex-vivo expanded Tregs, resulted in prolonged donor skin graft acceptance. These results are encouraging for the future of xenotransplantation tolerance.

CITATION INFORMATION: Stern J, Kofman S, Alonso-Guallart P, Berglund E, Danton M, Weiner J, Ayares D, Hawley R, Yamada K, Sachs D, Sykes M, Griesemer A. Autologous Expanded Tregs and Porcine Hematopoietic Cells to Prolong Xenogeneic Pig Skin Graft Acceptance in Baboons. Am J Transplant. 2017;17 (suppl 3).

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