Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates.

Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates.
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DOI:
10.1016/j.xcrm.2023.100959
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发表时间:
2023-03-21
影响因子:
14.3
通讯作者:
Lei, Ji
Lei, Ji
中科院分区:
医学1区
文献类型:
--
作者:
Deng, Hongping;Zhang, Alexander;Pang, Dillon Ren Rong;Xi, Yinsheng;Yang, Zhihong;Matheson, Rudy;Li, Guoping;Luo, Hao;Lee, Kang M.;Fu, Qiang;Zou, Zhongliang;Chen, Tao;Wang, Zhenjuan;Rosales, Ivy A.;Peters, Cole W.;Yang, Jibing;Coronel, Maria M.;Yolcu, Esma S.;Shirwan, Haval;Garcia, Andres J.;Markmann, James F.;Lei, Ji

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将胰岛移植到肝脏的方法会在移植后立即造成超过50%的胰岛丢失,随着时间的推移,移植物会逐渐功能障碍,如果出现严重的并发症,如干细胞来源的胰岛(SC-Islets)移植物发生畸胎瘤,移植物就无法恢复。大网膜是临床胰岛移植有吸引力的肝外替代部位。我们探索了一种将同种异体胰岛移植到大网膜的方法,在三种糖尿病非人类灵长类动物(NHP)中,大网膜是用血浆-凝血酶可生物降解的基质进行生物工程的。在移植后1周内,每个移植的NHP都达到正常血糖和胰岛素独立,并保持稳定,直到实验结束。每一例都取得了成功,从一名NHP捐赠者那里回收了胰岛。组织学显示移植物有强大的血管重建和神经再支配。这项临床前研究可以为β细胞替代策略的发展提供信息,包括在临床环境中使用SC-胰岛或其他类型的新型细胞。使用严格的类人糖尿病模型来研究胰岛在大网膜内的植入血浆-凝血酶矩阵工程师将大网膜移植到一个友好的细胞移植部位,将胰岛移植到生物工程大网袋中可以重新血运和重新支配单一供体移植的结果,完全正常血糖和胰岛素非依赖性邓等人。报道称,将胰岛移植到生物工程的大网膜袋中,可以在糖尿病非人类灵长类动物中实现完全的正常血糖和胰岛素独立。这项临床前研究可以促进β细胞替代策略的发展,包括在临床环境中使用干细胞来源的胰岛或其他类型的新型细胞。
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs). Within 1 week posttransplant, each transplanted NHP achieves normoglycemia and insulin independence and remains stable until termination of the experiment. Success was achieved in each case with islets recovered from a single NHP donor. Histology demonstrates robust revascularization and reinnervation of the graft. This preclinical study can inform the development of strategies for β cell replacement including the use of SC-islets or other types of novel cells in clinical settings. Use a stringent human-like diabetic model to study islet engraftment in the omentum Plasma-thrombin matrix engineers the omentum to a hospitable site for cell transplant Islets transplanted to a bioengineered omental pouch can revascularize and reinnervate Single donor transplantation results in full euglycemia and insulin independence Deng et al. report that transplanting islets onto a bioengineered omental pouch achieves full euglycemia and insulin independence in diabetic non-human primates. This preclinical study can facilitate the development of strategies for β cell replacement including the use of stem cell-derived islets or other types of novel cells in clinical settings.
工程人类干细胞衍生的胰岛逃避免疫排斥并促进局部免疫耐受性。
DOI: 10.1016/j.xcrm.2022.100879
发表时间: 2023-01-17
影响因子: 14.3
作者:
Gerace, Dario;Zhou, Qua;Kenty, Jennifer Hyoje-Ryu;Veres, Adrian;Sintov, Elad;Wang, Xi;Boulanger, Kyle R.;Li, Hongfei;Melton, Douglas A.
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DOI: 10.1111/j.1600-6143.2011.03683.x
发表时间: 2011-11
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:
Levesque V;Bardwell PD;Shimizu I;Haspot F;Benichou G;Yeap BY;Sykes M
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DOI: 10.1097/00007890-199309000-00007
发表时间: 1993-09-01
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
AO, ZL;MATAYOSHI, K;WARNOCK, GL
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DOI: 10.1126/sciadv.abm9881
发表时间: 2022-05-13
期刊: Science advances
影响因子: 13.6
作者:
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DOI: 10.1111/ajt.16875
发表时间: 2022-03
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:
Lei J;Zhang A;Deng H;Yang Z;Peters CW;Lee KM;Wang Z;Rosales IA;Rickert CG;Markmann JF
通讯作者: Markmann JF