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Chimeric Allografts Induced by Short‐Term Treatment With Stem Cell Mobilizing Agents Result in Long‐Term Kidney Transplant Survival Without Immunosuppression: II , Study in Miniature Swine
Author(s) -
Cameron A. M.,
Wesson R. N.,
Ahmadi A. R.,
Singer A. L.,
Hu X.,
Okabayashi T.,
Wang Y.,
Shigoka M.,
Fu Y.,
Gao W.,
Raccusen L. C.,
Montgomery R. A.,
Williams G. M.,
Sun Z.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13703
Subject(s) - immunosuppression , medicine , stem cell , transplantation , immunology , kidney , miniature swine , surgery , biology , genetics
Transplantation is now lifesaving therapy for patients with end‐stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor–recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well‐characterized large animal preclinical model. Here, we show that AMD 3100 and FK 506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug‐free long‐term survival in maximally immunologically mismatched swine. Three long‐term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years.