scholarly journals Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Min Cai ◽  
Rui Shen ◽  
Lei Song ◽  
Minjie Lu ◽  
Jianguang Wang ◽  
...  

Abstract Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

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.


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