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Erschienen in: Diabetologia 3/2014

01.03.2014 | Article

Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model

verfasst von: Danielle J. Borg, Marc Weigelt, Carmen Wilhelm, Michael Gerlach, Marc Bickle, Stephan Speier, Ezio Bonifacio, Angela Hommel

Erschienen in: Diabetologia | Ausgabe 3/2014

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Abstract

Aims/hypothesis

Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes. Successful outcomes are hampered by early islet beta cell loss. The adjuvant co-transplantation of mesenchymal stromal cells (MSCs) has the promise to improve islet transplant outcome.

Methods

We used a syngeneic marginal islet mass transplantation model in a mouse model of diabetes. Mice received islets or islets plus 250,000 MSCs. Kidney subcapsule, intra-hepatic and intra-ocular islet transplantation sites were used. Apoptosis, vascularisation, beta cell proliferation, MSC differentiation and laminin levels were determined by immunohistochemical analysis and image quantification post-transplant.

Results

Glucose homeostasis after the transplantation of syngeneic islets was improved by the co-transplantation of MSCs together with islets under the kidney capsule (p = 0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (p = 0.05). MSC co-transplantation resulted in reduced islet apoptosis, with reduced numbers of islet cells positive for cleaved caspase 3 being observed 14 days post-transplant. In kidney subcapsule, but not in intra-ocular islet transplant models, we observed increased re-vascularisation rates, but not increased blood vessel density in and around islets co-transplanted with MSCs compared with islets that were transplanted alone. Co-transplantation of MSCs did not increase beta cell proliferation, extracellular matrix protein laminin production or alpha cell numbers, and there was negligible MSC transdifferentiation into beta cells.

Conclusions/interpretation

Co-transplantation of MSCs may lead to improved islet function and survival in the early post-transplantation period in humans receiving islet transplantation.
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Metadaten
Titel
Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model
verfasst von
Danielle J. Borg
Marc Weigelt
Carmen Wilhelm
Michael Gerlach
Marc Bickle
Stephan Speier
Ezio Bonifacio
Angela Hommel
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 3/2014
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-3109-4

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