Back to Search
Start Over
Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model.
- 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=ā0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (pā=ā0.05). 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.
- Subjects :
- Animals
Blood Glucose
Cell Proliferation
Coculture Techniques
Diabetes Mellitus, Experimental immunology
Insulin Secretion
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic
Transplantation, Isogeneic
Diabetes Mellitus, Experimental pathology
Insulin metabolism
Islets of Langerhans metabolism
Islets of Langerhans Transplantation
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells metabolism
Subjects
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