Streptozotocin-induced diabetic rat-derived bone marrow mesenchymal stem cells have impaired abilities in proliferation, paracrine, antiapoptosis, and myogenic differentiation.
BACKGROUND
Diabetes has been widely recognized as a major risk factor for cardiovascular disease. With the development of the regenerative medicine, autologous bone marrow-derived mesenchymal stem cells (BMSCs), transplantation can effectively improve cardiac function after myocardial infarction. However, the BMSCs used in most previous studies are derived from young or normal donors. Little is know about the biological characters change of BMSCs in diabetes mellitus.


METHODS
BMSCs were taken from the streptozotocin (STZ)-induced diabetic rats and normal control rats. Cell proliferation was evaluated by CCK-8 assay. Production of vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 were measured by enzyme-linked immunosorbent assay. Apoptosis under hypoxia and serum deprivation culture conditions were detected by Hoechst 33342 stain and flow cytometry. Myogenic differentiation, induced by 5-azacytidine was assessed by using immunocytochemical staining for the expression of sarcomeric α-actin and desmin.


RESULTS
Diabetic rat models were successfully induced by intraperitoneal injection of STZ. The proliferative abilities of BMSCs derived from diabetic rats decreased significantly compared with that from normal rats (P < .05). Similar results were also presented in the cytokines (VEGF and IGF-1) release (P = .02 and P < .01, respectively) that the ability of antiapoptosis and myogenic differentiation decreased obviously between diabetes group and the normal control group (P < .01).


CONCLUSIONS
BMSCs from STZ-induced diabetic rats could be successfully harvested and expanded in vitro culture condition; their morphology was very similar to normal control group, with minor changes. However, the proliferative and differentiation properties of diabetic BMSCs, as well as cytokine release and antiapoptosis ability, were significantly impaired.
Jin
P
P
Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital of Wenzhou Medical College, People's Republic of China.
Zhang
X
X
Wu
Y
Y
Li
L
L
Yin
Q
Q
Zheng
L
L
Zhang
H
H
Sun
C
C
D000818:Animals; D017209:Apoptosis; D001374:Azacitidine / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D002875:Chromosomes / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D012307:Risk Factors
D001374:Azacitidine