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

IF 3.3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Xenotransplantation Pub Date : 2023-03-01 DOI:10.1111/xen.12793

Karen L Seeberger, Bassem F Salama, Sandra Kelly, Mandy Rosko, Chelsea Castro, Jessica DesAulniers, Gregory S Korbutt

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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.

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新生儿猪胰岛叶内内分泌和祖细胞的异质表达-对新生儿猪胰岛异种移植的意义。

新生儿猪胰岛(npi)是异种移植的一个胰岛来源。在猪中，胰叶是分开的，因此，在优化NPI分离时，应指定胰消化液中包含的胰叶。这些叶分别是十二指肠叶(DL)、脾叶(SL)和连接叶(CL)，分别与人胰腺的头、体尾和钩突相对应。在这项研究中，我们首次评估了所有三个新生儿猪胰腺叶和从这些胰腺叶中分离的npi。我们报道，在DL和CL中，叶之间的内分泌和祖细胞组成有显著差异，并且在外分泌管周围的间质内观察到胰管腺(PDG)。体外分化后，从各叶分离的npi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，移植了从SL分离的npi的糖尿病免疫缺陷小鼠早在4周就表现出良好的血糖控制(p < 0.05)，并在移植后6周达到正常血糖(p < 0.01)。我们首次报道了新生儿猪胰腺叶之间的显著差异，并证明这些胰腺叶的npi在异种移植功能上存在差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Xenotransplantation 医学-医学：研究与实验

CiteScore

6.80

自引率

15.40%

发文量

审稿时长

>12 weeks

期刊介绍： Xenotransplantation provides its readership with rapid communication of new findings in the field of organ and tissue transplantation across species barriers.The journal is not only of interest to those whose primary area is xenotransplantation, but also to veterinarians, microbiologists and geneticists. It also investigates and reports on the controversial theological, ethical, legal and psychological implications of xenotransplantation.