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Diabetologia
Published in: Diabetologia 1/2017

Open Access 01-01-2017 | Article

Human multipotent adult progenitor cells enhance islet function and revascularisation when co-transplanted as a composite pellet in a mouse model of diabetes

Authors: João Paulo M. C. M. Cunha, Gunter Leuckx, Peter Sterkendries, Hannelie Korf, Gabriela Bomfim-Ferreira, Lutgart Overbergh, Bart Vaes, Harry Heimberg, Conny Gysemans, Chantal Mathieu

Published in: Diabetologia | Issue 1/2017

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Abstract

Aims/hypothesis

Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival.

Methods

Islets (150) were co-transplanted, with or without human MAPCs (2.5 × 105) as separate or composite pellets, under the kidney capsule of syngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels were frequently monitored and IPGTTs were carried out. Grafts and serum were harvested at 2 and 5 weeks after transplantation to assess outcome.

Results

Human MAPCs produced high amounts of angiogenic growth factors, including vascular endothelial growth factor, in vitro and in vivo, as demonstrated by the induction of neo-angiogenesis in the chorioallantoic membrane assay. Islet–human MAPC co-transplantation as a composite pellet significantly improved the outcome of islet transplantation as measured by the initial glycaemic control, diabetes reversal rate, glucose tolerance and serum C-peptide concentration compared with the outcome following transplantation of islets alone. Histologically, a higher blood vessel area and density in addition to a higher vessel/islet ratio were detected in recipients of islet–human MAPC composites.

Conclusions/interpretation

The present data suggest that co-transplantation of mouse pancreatic islets with human MAPCs, which secrete high amounts of angiogenic growth factors, enhance islet graft revascularisation and subsequently improve islet graft function.
Appendix
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Metadata
Title
Human multipotent adult progenitor cells enhance islet function and revascularisation when co-transplanted as a composite pellet in a mouse model of diabetes
Authors
João Paulo M. C. M. Cunha
Gunter Leuckx
Peter Sterkendries
Hannelie Korf
Gabriela Bomfim-Ferreira
Lutgart Overbergh
Bart Vaes
Harry Heimberg
Conny Gysemans
Chantal Mathieu
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 1/2017
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4120-3

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