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.
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.
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DOI：
10.1111/ajt.13706
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Sun Z
中科院分区：
文献类型：
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作者：
Hu X;Okabayashi T;Cameron AM;Wang Y;Hisada M;Li J;Raccusen LC;Zheng Q;Montgomery RA;Williams GM;Sun Z
移植耐受消除终身免疫抑制一直是60年来研究的目标。混合嵌合的诱导已显示出前景，并已成功地扩展到大型动物和临床。然而，它仍然很麻烦，需要大量的早期免疫抑制。在这里，我们报告了肾移植后第一周注射4次AMD3100 (A)，一种CXCR-4拮抗剂，加上8次低剂量FK506 （F， 0.05mg/kg/天）延长了生存期，但在30-90天发生肾功能衰竭死亡。在移植后1、2和3个月重复相同的A和F疗程，7个月时92%的异体移植接受率（n=12），肾脏功能和组织学正常，无需进一步治疗。移植接受与宿主干细胞的流入有关，导致混合肾脏和宿主免疫反应的调节。这些结果的证实可能会引发移植后治疗的范式转变。
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.