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一种用于研究移植胰岛血管化的新型离体方法。

A Novel ex vivo Method for Investigating Vascularization of Transplanted Islets.

机构信息

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA.

出版信息

J Vasc Res. 2022;59(4):229-238. doi: 10.1159/000523925. Epub 2022 Apr 22.

DOI:10.1159/000523925
PMID:35462373
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9308658/
Abstract

Revascularization of transplanted pancreatic islets is critical for survival and treatment of type 1 diabetes. Questions concerning how islets influence local microvascular networks and how networks form connections with islets remain understudied and motivate the need for new models that mimic the complexity of real tissue. Recently, our laboratory established the rat mesentery culture model as a tool to investigate cell dynamics involved in microvascular growth. An advantage is the ability to observe blood vessels, lymphatics, and immune cells. The objective of this study was to establish the rat mesentery tissue culture model as a useful tool to investigate islet tissue integration. DiI-labeled islets were seeded onto adult rat mesentery tissues and cultured for up to 3 days. Live lectin labeling enabled time-lapse observation of vessel growth. During culture, DiI-positive islets remained intact. Radial lectin-positive capillary sprouts with DiI labeling were observed to form from islets and connect to host networks. Lectin-positive vessels from host networks were also seen growing toward islets. PECAM and NG2 labeling confirmed that vessels sprouting from islets contained endothelial cells and pericytes. Our results introduce the rat mesentery culture model as a platform for investigating dynamics associated with the initial revascularization of transplanted islets.

摘要

移植胰岛的再血管化对于 1 型糖尿病的治疗和生存至关重要。关于胰岛如何影响局部微血管网络以及网络如何与胰岛建立连接的问题仍未得到充分研究,这促使我们需要建立新的模型来模拟真实组织的复杂性。最近,我们实验室建立了大鼠肠系膜培养模型,作为研究与微血管生长相关的细胞动力学的工具。该模型的一个优势是能够观察血管、淋巴管和免疫细胞。本研究的目的是建立大鼠肠系膜组织培养模型,作为研究胰岛组织整合的有用工具。将 DiI 标记的胰岛接种到成年大鼠肠系膜组织上,并培养长达 3 天。活体凝集素标记可实现对血管生长的延时观察。在培养过程中,DiI 阳性胰岛保持完整。观察到带有 DiI 标记的放射状凝集素阳性毛细血管芽从胰岛中形成并与宿主网络连接。也观察到来自宿主网络的凝集素阳性血管向胰岛生长。PECAM 和 NG2 标记证实,从胰岛中长出的血管含有内皮细胞和周细胞。我们的研究结果表明,大鼠肠系膜培养模型是研究移植胰岛初始再血管化相关动力学的平台。

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引用本文的文献

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Islet dimension and its impact on transplant outcome: A systematic review.胰岛大小及其对移植结果的影响:一项系统综述。
World J Transplant. 2025 Sep 18;15(3):102383. doi: 10.5500/wjt.v15.i3.102383.

本文引用的文献

1
Brain capillary pericytes exert a substantial but slow influence on blood flow.脑毛细血管周细胞对血流有显著但缓慢的影响。
Nat Neurosci. 2021 May;24(5):633-645. doi: 10.1038/s41593-020-00793-2. Epub 2021 Feb 18.
2
Contractile pericytes determine the direction of blood flow at capillary junctions.收缩性周细胞决定毛细血管连接处的血流方向。
Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):27022-27033. doi: 10.1073/pnas.1922755117. Epub 2020 Oct 13.
3
Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.
从器官捐献者获取的胰腺组织切片可实现 1 型糖尿病发病机制的原位分析。
JCI Insight. 2020 Apr 23;5(8):134525. doi: 10.1172/jci.insight.134525.
4
A novel tissue culture model for evaluating the effect of aging on stem cell fate in adult microvascular networks.一种新型的组织培养模型,用于评估衰老对成年微血管网络中干细胞命运的影响。
Geroscience. 2020 Apr;42(2):515-526. doi: 10.1007/s11357-020-00178-0. Epub 2020 Mar 23.
5
Evaluating Vascularization of Heterotopic Islet Constructs for Type 1 Diabetes Using an In Vitro Platform.利用体外平台评估用于 1 型糖尿病的异位胰岛构建物的血管化。
Integr Biol (Camb). 2019 Nov 30;11(8):331-341. doi: 10.1093/intbio/zyz027.
6
Microvessel Network Formation and Interactions with Pancreatic Islets in Three-Dimensional Chip Cultures.三维芯片培养中的微血管网络形成及与胰岛的相互作用。
Tissue Eng Part A. 2020 May;26(9-10):556-568. doi: 10.1089/ten.TEA.2019.0186. Epub 2020 Jan 20.
7
Recruited fibroblasts reconstitute the peri-islet membrane: a longitudinal imaging study of human islet grafting and revascularisation.招募的成纤维细胞重建胰岛周围膜:一项人类胰岛移植和再血管化的纵向成像研究。
Diabetologia. 2020 Jan;63(1):137-148. doi: 10.1007/s00125-019-05018-1. Epub 2019 Nov 7.
8
Bioreactor System to Perfuse Mesentery Microvascular Networks and Study Flow Effects During Angiogenesis.生物反应器系统用于灌注肠系膜微血管网络,并在血管生成过程中研究血流效应。
Tissue Eng Part C Methods. 2019 Aug;25(8):447-458. doi: 10.1089/ten.TEC.2019.0119.
9
Nerve/glial antigen 2 is crucially involved in the revascularization of freely transplanted pancreatic islets.神经胶质抗原 2 对于游离移植胰岛的再血管化至关重要。
Cell Tissue Res. 2019 Nov;378(2):195-205. doi: 10.1007/s00441-019-03048-0. Epub 2019 May 27.
10
Pancreatic Pericytes in Glucose Homeostasis and Diabetes.胰腺周细胞在葡萄糖稳态和糖尿病中的作用。
Adv Exp Med Biol. 2019;1122:27-40. doi: 10.1007/978-3-030-11093-2_2.