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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: I Study in Rats #MMPMID26749344
Hu X; Okabayashi T; Cameron AM; Wang Y; Hisada M; Li J; Raccusen LC; Zheng Q; Montgomery RA; Williams GM; Sun Z
Am J Transplant 2016[Jul]; 16 (7): 2055-65 PMID26749344show ga
Transplant tolerance allowing the elimination of life long immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been successfully extended to large animals and the clinic. However, it remains cumbersome and requires heavy early immunosuppression. Here, we report that 4 injections of AMD3100 (A), a CXCR-4 antagonist, plus 8 injections of low-dose FK506 (F, 0.05mg/kg/day) first week after kidney transplantation extended survival, but death from renal failure occurred at 30?90 days. Repeating the same course of A and F at 1, 2 and 3 months after transplant resulted in 92% allograft acceptance (n=12) at 7 months, 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 post-transplant therapy.