Reduced Population and Impaired Osteogenic Potential of Bone Marrow-Derived Mesenchymal Stem Cells in Streptozocin-Induced Diabetic Rats

Abstract

Cell therapy using mesenchymal stein cells(MSCs) from different donors is considered a promising therapeutic method for a variety of diseases. However, the possibility of donor-specific variations in the biological characteristics of MSCs requires further elucidation to ensure their optimal clinical usages. The authors examined the isolation yields and osteogenic potentials of bone marrow derived MSCs from diabetic rats to investigate the notion that diabetes adversely affects the functions of MSCs. Sprague-Dawley rats with and without streptozocin induced diabetes were followed for 3 weeks and allocated to a tightly controlled group(TDR), a poorly controlled group(PDR), or to a non-streptozocin-treated normal control group(CR). Isolation yields and the osteogenic differentiation potentials of MSCs from bone marrow were then assayed. Numbers of colony forming unit-fibroblasts(CFU-Fs) and alkaline phosphatase(ALP) positive CFU-Fs were significantly lower in the PDR group than in the other groups. During osteogenic differentiation, cell proliferation rates and ALP activities were not significantly different in the three groups, whereas calcium contents, numbers of bone nodules, and osteocalcin mRNA levels were significantly lower in the PDR group. Our study demonstrates that MSCs isolation yields and osteogenic potentials are lower in diabetic rats, and suggests that the presence of diabetes be considered when selecting MSC donors.