Background: To assess the effects of intrahepatic autotransplantation of bone-derived Beagle canine mesenchymal stem cells (BcMSCs) containing human insulin and EGFP in diabetic Beagle dogs.
Materials and methods: BcMSCs were isolated from Beagle canine bone marrow, expanded, and transfected with a recombinant retrovirus MSCV carrying human insulin and EGFP. Animals were made diabetic by an intravenous administration of streptozotocin (STZ, 30 mg/kg) and alloxan (50 mg/kg), followed by intrahepatic autotransplantation of transfected BcMSCs. The variations of body weight, blood glucose, serum insulin levels, and plasma C-peptide were determined after autotransplantation. BcMSCs' survival and human insulin expression in liver and serum were examined by fluorescent microscopy, radioimmunoassay (RIA), and immunohistochemistry (IHC).
Results: The body weight of diabetic Beagle dogs received BcMSCs transplantation increased by 11.09% within 16 wk after treatment, and the average blood glucose levels were 19.80±3.13 mmol/L (d 7) and 9.78±3.11 mmol/L (d 112), while in untreated animals, the average values were 21.20±3.26 mmol/L (d 7) and 22.5±3.22 mmol/L (d 112), showing a significant difference (P<0.05). The detection of C-peptide excluded the possible function of regenerative β cells. However, glucose tolerance test revealed BcMSCs group response was not as efficient as that of normal islets, although they could respond to the glucose challenge.
Conclusion: Experimental diabetes could be relieved effectively for up to 16 wk by intrahepatic autotransplantation of BcMSCs expressing human insulin, which implies a novel approach of gene therapy for type I diabetes.
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