Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy

Abstract

AbstractBackground: Diabetic cardiomyopathy (DCM) is a serious health-threatening diabetic complication characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are considered as a potential therapeutic tool for DCM and myocardial fibrosis via the regulation of microRNA (miRNA) expression. This study aimed to investigate the therapeutic effects of tail vein injection of hUC-MSCs on DCM and determine effects on miRNA and target mRNA expression. Methods: A DCM mouse model was induced by multiple low-dose streptozotocin (STZ) injections and the effect of hUC-MSCs administration was assessed at two time points, 10 and 18 weeks after induction of diabetes mellitus. Analysis of mouse heart tissues was undertaken two weeks after tail vein injection of hUC-MSCs. Biochemical methods, echocardiography, histopathology and polymerase chain reaction (PCR) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis, and expression of fibrosis related mRNA and miRNA. Results: DCM animals treated with saline had impaired cardiac function, increased fibrosis and decreased expression of miRNA-133a after 10 and 18 weeks of DM. The myocardial fibrosis and cardiac dysfunction induced in DCM mice were significantly improved 2 weeks after hUC-MSCs treatment at both an early and late disease time point. Furthermore, pro-fibrotic indicators such as α-SMA, collagen I, collagen III, Smad3, and Smad4 levels were significantly reduced after hUC-MSCs infusion compared with DCM hearts from animals treated with normal saline, and anti-fibrotic indicators such as FGF1 and miRNA-133a were significantly increased. Conclusion: These results suggest that hUC-MSCs may improve cardiac function and myocardial fibrosis in DCM by regulating miRNA-133a and fibrosis related mRNAs.