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生物工程化大网膜移植部位可促进非人类灵长类动物胰岛同种异体移植物的存活。

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

机构信息

Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

School of Clinical Medicine, Southern Medical University, Foshan 528300, China.

出版信息

Cell Rep Med. 2023 Mar 21;4(3):100959. doi: 10.1016/j.xcrm.2023.100959. Epub 2023 Mar 1.

Abstract

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.

摘要

胰岛移植到肝脏的方法存在一个问题,即胰岛在移植后立即损失超过 50%,随着时间的推移,移植物的功能逐渐下降,如果发生严重并发症,如源自干细胞的胰岛(SC-胰岛)的畸胎瘤,移植物将无法恢复。大网膜具有作为临床胰岛移植的有吸引力的肝外替代部位。我们探索了一种方法,即将同种异体胰岛移植到大网膜上,大网膜用等离子体-凝血酶可生物降解基质进行生物工程化处理,在三只糖尿病非人类灵长类动物(NHPs)中进行。在移植后 1 周内,每个接受移植的 NHP 动物均实现正常血糖和胰岛素独立性,并保持稳定,直到实验结束。在每种情况下,均从单个 NHP 供体中回收胰岛获得成功。组织学显示移植物有强大的再血管化和再神经支配。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/458c/10040375/a34050654277/fx1.jpg

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