Composite Islet-Kidneys From Single Baboon Donors Cure Diabetes Across Fully Allogenic Barriers
Composite Islet-Kidneys From Single Baboon Donors Cure Diabetes Across Fully Allogenic Barriers
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DOI：
10.1111/j.1600-6143.2011.03733.x
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发表时间：
2011-12-01
影响因子：
8.8
通讯作者：
Sachs, D. H.
中科院分区：
文献类型：
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作者：
Yamada, K.;Hirakata, A.;Sachs, D. H.
我们以前曾报道，移植（Tx）的预血管化供体胰岛复合胰岛肾（IK）逆转糖尿病高血糖小型猪。为了测试这种策略的潜在临床适用性，我们将其扩展到完全同种异体的非人灵长类动物模型。通过从50%至70%的部分胰腺切除术中分离胰岛并将其注射到自体肾包膜下，在同种异体Tx之前允许血管化，在狒狒中制备IKs。通过立体脲佐菌素或全胰腺切除术诱导糖尿病的狒狒接受复合IKs（n = 3）或肾包膜下或门静脉内（n = 3）游离胰岛，通过完全同种异体屏障，采用由ATG随后MMF和他克莫司组成的免疫抑制方案。两个IK受体的FBS在Tx后立即下降，并且在整个实验期间（225和301天）不需要胰岛素治疗。相比之下，所有异体游离胰岛的接受者显示不稳定的FBS水平，并在2个月内需要胰岛素。我们的结论是，除了维持肌酐在正常范围内，完全同种异体IKs从单一的灵长类动物捐赠者可以实现葡萄糖调节，而没有胰岛素治疗，而游离胰岛没有。这些结果支持复合同种异体IK Tx作为终末期糖尿病肾病的潜在治疗的可行性。
We have previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reverses diabetic hyperglycemia in miniature swine. In order to test the potential clinical applicability of this strategy, we have extended it to a fully allogeneic nonhuman primate model. IKs were prepared in baboons by isolating islets from 50% to 70% partial pancreatectomies and injecting them under the autologous renal capsule, allowing vascularization before allogeneic Tx. Baboons with diabetes induced by stereptozotocin or total pancreatectomy, received composite IKs (n = 3) or free islets under the renal capsule or intraportally (n = 3), across fully allogeneic barriers with an immunosuppressive regimen consisting of ATG followed by MMF and tacrolimus. FBS of two of IK recipients decreased immediately after Tx and no insulin therapy was required throughout the experimental period (225 and 301 days). In contrast, all recipients of allogeneic free islets showed unstable FBS levels and required insulin within 2 months. We conclude that in addition to maintaining creatinine in the normal range, fully allogeneic IKs from single primate donors can achieve glucose regulation without insulin therapy, while free islets do not. These results support the feasibility of composite allogeneic IK Tx as a potential cure for end-stage diabetic nephropathy.