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Recruited fibroblasts reconstitute the peri-islet membrane: a longitudinal imaging study of human islet grafting and revascularisation.

Abstract：

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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Nilsson J,Fardoos R,Hansen L,Lövkvist H,Pietras K,Holmberg D,Schmidt-Christensen A

doi

10.1007/s00125-019-05018-1

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

137-148

issue

1

eissn

0012-186X

issn

1432-0428

pii

10.1007/s00125-019-05018-1

journal_volume

63

pub_type

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