Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.
Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys.
复制标题
DOI：
10.1111/ajt.13952
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Yamada K
中科院分区：
文献类型：
--
作者：
Pathiraja V;Villani V;Tasaki M;Matar AJ;Duran-Struuck R;Yamada R;Moran SG;Clayman ES;Hanekamp J;Shimizu A;Sachs DH;Huang CA;Yamada K
我们以前曾报道，移植(TX)无血管供体胰岛作为复合胰岛-肾脏(IK)可以逆转小型猪和狒狒的糖尿病高血糖。为了增强这一策略的潜在临床适用性，我们现在将这一方法与造血干细胞(HSC)TX结合起来，试图在非人类灵长类动物中诱导耐受。从70%的胰腺部分切除术中分离胰岛，并将其注入5只供体恒河猴的自体肾被膜下，至少在同种异体IKTx移植前3个月制备IKs。HSCTx是在对供者进行动员和白细胞分离，并对受者进行全身照射、T细胞去除和环孢素处理后进行的。其中一例用于组织学分析，四例移植到糖尿病患者体内。于HSCTx后20~22天(n=3)或208天(n=1)行IKTx。所有动物均接受iKs，无排斥反应。所有受试者在IKTx之前每天需要20U的胰岛素以维持低于200 mg/dl，而在IKTx之后，3只动物需要最小剂量的胰岛素(1-3U/天)，其中一只动物没有胰岛素。这些结果构成了一个原则证明，即这种IK耐受策略可以在不需要免疫抑制的情况下治愈终末期肾脏疾病和糖尿病。
We have previously reported that transplantation (Tx) of prevascularized donor islets as composite Islet-Kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cells (HSC) Tx in an attempt to induce tolerance in non-human primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IKTx. HSCTx was performed following mobilization and leukapheresis of the donors, and conditioning of the recipients with total body irradiation, T-cell depletion and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IKTx was performed either 20–22 (n=3) or 208 (n=1) days after HSCTx. All animals accepted IKs without rejection. All recipients required >20 U/day of insulin before IKTx to maintain less than 200mg/dl, whereas after IKTx 3 animals required minimal doses of insulin (1–3 U/day) and one animal was insulin-free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression.
登录
查看更多内容
DOI：
10.1111/ajt.13952
发表时间：
2017-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Pathiraja V;Villani V;Tasaki M;Matar AJ;Duran-Struuck R;Yamada R;Moran SG;Clayman ES;Hanekamp J;Shimizu A;Sachs DH;Huang CA;Yamada K
通讯作者：
Yamada K
影响因子：
82.9
作者：
Yamada, K;Yazawa, K;Sachs, DH
通讯作者：
Sachs, DH
影响因子：
6.2
作者：
Yamada, K;Vagefi, PA;Sachs, DH
通讯作者：
Sachs, DH
DOI：
10.1073/pnas.0306666101
发表时间：
2004-03-16
影响因子：
11.1
作者：
Kamano, C;Vagefi, PA;Yamada, K
通讯作者：
Yamada, K
影响因子：
4.4
作者：
Yamada, K;Shimizu, A;Sachs, DH
通讯作者：
Sachs, DH