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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: A Study in Rats
Author(s) -
Hu X.,
Okabayashi T.,
Cameron A. M.,
Wang Y.,
Hisada M.,
Li J.,
Raccusen L. C.,
Zheng Q.,
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.13706
Subject(s) - immunosuppression , medicine , transplantation , kidney , kidney transplantation , immunology , urology
Transplant tolerance allowing the elimination of lifelong immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been extended successfully to large animals and to the clinic; however, it remains cumbersome and requires heavy early immunosuppression. In this study, we reported that four injections of AMD 3100, a CXCR 4 antagonist, plus eight injections of low‐dose FK 506 (0.05 mg/kg per day) in the first week after kidney transplantation extended survival, but death from renal failure occurred at 30–90 days. Repeating the same course of AMD 3100 and FK 506 at 1, 2 and 3 mo after transplant resulted in 92% allograft acceptance (n = 12) at 7 mo, normal kidney function and histology with no further treatment. Transplant acceptance was associated with the influx of host stem cells, resulting in a hybrid kidney and a modulated host immune response. Confirmation of these results could initiate a paradigm shift in posttransplant therapy.