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新生猪胰腺小叶内内分泌和祖细胞的异质性表达——对新生猪胰岛异种移植的影响。

Heterogenous expression of endocrine and progenitor cells within the neonatal porcine pancreatic lobes-Implications for neonatal porcine islet xenotransplantation.

机构信息

Alberta Diabetes Institute and Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Xenotransplantation. 2023 Mar;30(2):e12793. doi: 10.1111/xen.12793. Epub 2023 Feb 7.

Abstract

Neonatal porcine islets (NPIs) are a source of islets for xenotransplantation. In the pig, the pancreatic lobes remain separate, thus, when optimizing NPI isolation, the pancreatic lobes included in the pancreatic digest should be specified. These lobes are the duodenal (DL), splenic (SL) and connecting (CL) lobe that correspond to the head, body-tail, and uncinate process of the human pancreas. In this study we are the first to evaluate all three neonatal porcine pancreatic lobes and NPIs isolated from these lobes. We report, a significant difference in endocrine and progenitor cell composition between lobes, and observed pancreatic duct glands (PDG) within the mesenchyme surrounding exocrine ducts in the DL and CL. Following in vitro differentiation, NPIs isolated from each lobe differed significantly in the percent increase of endocrine cells and final cell composition. Compared to other recipients, diabetic immunodeficient mice transplanted with NPIs isolated from the SL demonstrated euglycemic control as early as 4 weeks (p < 0.05) and achieved normoglycemia by 6 weeks post-transplant (p < 0.01). For the first time we report significant differences between the neonatal porcine pancreatic lobes and demonstrate that NPIs from these lobes differ in xenograft function.

摘要

新生猪胰岛(NPIs)是异种移植胰岛的来源。在猪中,胰腺叶保持独立,因此,在优化 NPI 分离时,应指定包含在胰腺消化物中的胰腺叶。这些叶是十二指肠(DL)、脾(SL)和连接(CL)叶,分别对应于人胰腺的头部、体尾和钩突。在这项研究中,我们首次评估了来自这三个叶的所有新生猪胰腺叶和 NPIs。我们报告说,叶之间的内分泌和祖细胞组成存在显著差异,并观察到在 DL 和 CL 的外分泌导管周围的间质中存在胰腺导管腺(PDG)。在体外分化后,从每个叶分离的 NPIs 在内分泌细胞的百分比增加和最终细胞组成方面存在显著差异。与其他受体相比,接受来自 SL 的 NPIs 移植的糖尿病免疫缺陷小鼠早在 4 周(p < 0.05)就表现出血糖控制正常,并在移植后 6 周(p < 0.01)达到正常血糖水平。我们首次报告了新生猪胰腺叶之间的显著差异,并证明来自这些叶的 NPIs 在异种移植物功能方面存在差异。

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