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Recruited fibroblasts reconstitute the peri-islet membrane: a longitudinal imaging study of human islet grafting and revascularisation.
Diabetologia ( IF 8.2 ) Pub Date : 2019-11-07 , DOI: 10.1007/s00125-019-05018-1
Julia Nilsson 1, 2 , Rabiah Fardoos 1 , Lisbeth Hansen 1 , Håkan Lövkvist 3, 4 , Kristian Pietras 5 , Dan Holmberg 1, 2 , Anja Schmidt-Christensen 1, 2
Affiliation  

AIMS/HYPOTHESIS Rapid and adequate islet revascularisation and restoration of the islet-extracellular matrix (ECM) interaction are significant factors influencing islet survival and function of the transplanted islets in individuals with type 1 diabetes. Because the ECM encapsulating the islets is degraded during islet isolation, understanding the process of revascularisation and engraftment after transplantation is essential and needs further investigation. METHODS Here we apply a longitudinal and high-resolution imaging approach to investigate the dynamics of the pancreatic islet engraftment process up to 11 months after transplantation. Human and mouse islet grafts were inserted into the anterior chamber of the mouse eye, using a NOD.ROSA-tomato.Rag2-/- or B6.ROSA-tomato host allowing the investigation of the expansion of host vs donor cells and the contribution of host cells to aspects such as promoting the encapsulation and vascularisation of the graft. RESULTS A fibroblast-like stromal cell population of host origin rapidly migrates to ensheath the transplanted islet and aid in the formation of a basement membrane-like structure. Moreover, we show that the vessel network, while reconstituted by host endothelial cells, still retains the overall architecture of the donor islets. CONCLUSIONS/INTERPRETATION In this transplantation situation the fibroblast-like stromal cells appear to take over as main producers of ECM or act as a scaffold for other ECM-producing cells to reconstitute a peri-islet-like basement membrane. This may have implications for our understanding of long-term graft rejection and for the design of novel strategies to interfere with this process.

中文翻译:

募集的成纤维细胞重建了胰岛周膜:人类胰岛移植和血运重建的纵向成像研究。

目的/假说快速和充分的胰岛血运重建以及胰岛-细胞外基质(ECM)相互作用的恢复是影响1型糖尿病患者胰岛存活和胰岛功能的重要因素。由于封装胰岛的ECM在分离胰岛过程中会降解,因此了解移植后的血运重建和移植过程至关重要,需要进一步研究。方法在这里,我们采用纵向和高分辨率的成像方法来研究胰岛植入后长达11个月的动态。使用NOD.ROSA-tomato.Rag2-/-或B6将人和小鼠的胰岛移植物插入小鼠眼的前房。ROSA-番茄宿主可研究宿主细胞与供体细胞的扩增以及宿主细胞对促进移植物的封装和血管形成等方面的贡献。结果寄主来源的成纤维细胞样基质细胞群迅速迁移到被移植的胰岛,并帮助形成了基底膜样结构。此外,我们显示血管网络虽然由宿主内皮细胞重建,但仍保留了供体胰岛的整体结构。结论/解释在这种移植情况下,成纤维细胞样基质细胞似乎取代了ECM的主要生产者,或充当其他ECM产生细胞的支架,以重建胰岛样基底膜。
更新日期:2019-11-07
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