Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats

Jun 18, 2013Biochemical and biophysical research communications

Repeated bone marrow stem cell infusions lower high blood sugar in rats with type 2 diabetes

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Abstract

Three infusions of mesenchymal stem cells resulted in sustained normalization of blood sugar levels in type 2 diabetes rats for at least 9 weeks.

Single infusions of mesenchymal stem cells only temporarily reduced hyperglycemia in early-phase type 2 diabetes rats.
Three or more infusions were necessary to achieve and maintain normal blood sugar levels.
Increased serum levels of insulin and C-peptide were observed following multiple stem cell infusions.
Improved glucose metabolism was confirmed through oral glucose tolerance tests after the treatments.
Restoration of pancreatic islet structure and number was noted after multiple stem cell infusions.

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The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 × 10(6)cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (1 week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients.

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Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats

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