Effect of Bone Marrow Mesenchymal Stem Cells (BMSCs) on Cardiac Function and Ventricular Remodeling in Diabetic Rat Models Through Inhibiting MicroRNA (miR)-34a

2021 ◽  
Vol 11 (8) ◽  
pp. 1490-1496
Author(s):  
Xiangzhen Qu ◽  
Shanyong Zhu

Diabetes mellitus (DM) is harmful to heart tissue. We transplanted bone marrow mesenchymal stem cells (BMSCs) in this study to improve the function of diabetic heart. 45 rats were divided into healthy group, DM group (treated with high-fat diet), and BMSCs group (BMSCs transplantation into the ventricular wall) followed by analysis of miR-34a and aldehyde dehydrogenase 2 (ALDH2) levels, heart function, and ventricular remodeling in the three groups of rats. BMSCs were successfully cultured with high purity, and the myocardium in the BMSCs group was successfully labeled by DAPI. The left ventricular hypertrophy index and myocardial tissue CVF of rats with DM increased significantly, suggesting that ventricular remodeling in DM rats was stimulated. However, when BMSCs were transplanted to the ventricular wall, although the ventricular remodeling was not completely avoided, apoptosis of BMSCs group was significantly reduced. MiR-34a relative level in BMSCs group was obviously elevated, whereas ALDH2 level showed opposite trend with a negative relationship. MiR-34a can effectively bind to the 3′-UTR of ALDH2 mRNA, indicating that it can directly regulate gene expression. BMSCs can promote the synthesis of ALDH2 by inhibiting the expression of miR-34a, and improve the cardiac function and ventricular remodeling of diabetic rats.

2016 ◽  
Vol 13 (6) ◽  
pp. 5317-5325 ◽  
Author(s):  
YUANFAN WU ◽  
JING ZHOU ◽  
LIQING BI ◽  
MIN HUANG ◽  
YI HAN ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
pp. 44-50
Author(s):  
Yongming He ◽  
Ping Li ◽  
Yunlong Chen ◽  
Youmei Li

Transplanted bone marrow mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes and may have the potential to replace necrotic cardiomyocytes resulting from myocardial infarction (MI). Here we established a method for transfection of MSCs with an expression vector encoding human vascular Eedothelial Ggowth Ffctor (hVEGF). We evaluated the impact of transplantation of transfected MSCs on the recovery cardiac function and angiogenesis in a rat model of MI. Rat MSCs were separated by density gradient centrifugation; their specific surface markers were examined as was their ability to differentiate. MSCs were then transfected with pcDNA 3.1-hVEGF 165 or control-containing liposomes. Rats in the experimental MI groups received transfected MSCs, MSCs alone, or gene-transfection alone; controls included a no intervention MI group and a group that was not subjected to ischemia. Among the results, MSCs were successfully isolated and cultured. Among the intervention groups, those that received transplantation of MSCs expressing hVEGF 165 included the smallest areas of infarction and demonstrated the best recovery of cardiac function overall. Moreover, capillary density detected in this group was significantly greater than in the control group and likewise greater than in rats transplanted with MSCs alone. BrdU and Troponin-T staining revealed differential increases in the number of viable cardiomyocytes within the infarction areas; some cardiomyocytes were double-positive. Likewise, evaluation using RT-PCR revealed higher expression levels of hVEGF in rats transplanted with transfected cells compared to those treated with gene transfection alone.


2021 ◽  
Author(s):  
Jing Liu ◽  
Xiaoting Liang ◽  
Mimi Li ◽  
Fang Lin ◽  
Xiaoxue Ma ◽  
...  

Abstract Background: Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods: HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function, angiogenesis, fibrosis and hypertrophy, and immune cells infiltration were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. Results: HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells in the heart with HucMSC than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in the HucMSCs treated heart compared to the control. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or C-C Motif Chemokine receptor 5 (CCR5) antagonist significantly reversed this effect. Conclusion: These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ regulatory T cells and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.


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