Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
School of Clinical Medicine, Southern Medical University, Foshan 528300, China.
Cell Rep Med. 2023 Mar 21;4(3):100959. doi: 10.1016/j.xcrm.2023.100959. Epub 2023 Mar 1.
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.
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。