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

Authors :
Borg DJ
Weigelt M
Wilhelm C
Gerlach M
Bickle M
Speier S
Bonifacio E
Hommel A
Source :
Diabetologia [Diabetologia] 2014 Mar; Vol. 57 (3), pp. 522-31. Date of Electronic Publication: 2013 Nov 20.
Publication Year :
2014

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.<br />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.<br />Results: Glucose homeostasis after the transplantation of syngeneic islets was improved by the co-transplantation of MSCs together with islets under the kidney capsule (pā€‰=ā€‰0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (pā€‰=ā€‰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.<br />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.

Details

Language :
English
ISSN :
1432-0428
Volume :
57
Issue :
3
Database :
MEDLINE
Journal :
Diabetologia
Publication Type :
Academic Journal
Accession number :
24253203
Full Text :
https://doi.org/10.1007/s00125-013-3109-4