c-kit+VEGFR-2+ Mesenchymal Stem Cells Differentiate into Cardiovascular Cells and Repair Infarcted Myocardium after Transplantation

• Published in: Stem cell reviews and reports 2023-01, Vol.19 (1), p.230-247
• Main Authors: Zhou, Pei, Yu, Shu-na, Zhang, Hai-feng, Wang, Yong-li, Tao, Ping, Tan, Yu-zhen, Wang, Hai-jie
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animal models; Animals; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Bone marrow; Bone marrow transplantation; Bone morphogenetic protein 2; c-Kit protein; Cardiac function; Cell Biology; Cell differentiation; Cell therapy; Coronary artery; Endothelium; Gene expression; Hypoxia; Ischemia; Life Sciences; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells; Myocardial Infarction; Myocardium; Myocardium - metabolism; Paracrine signalling; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Rats; Regeneration; Regenerative Medicine/Tissue Engineering; Smooth muscle; Stem cell transplantation; Stem Cells; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular endothelial growth factor receptors
• ISSN: 2629-3269; 2629-3277; 2629-3277
• DOI: 10.1007/s12015-022-10430-z

Resent study suggests that c-kit + cells in bone marrow-derived MSCs may differentiate toward cardiamyocytes. However, the properties of c-kit + MSCs remain unclear. This study isolated c-kit + VEGFR-2 + cells from rat bone marrow-derived MSCs, and assessed potential of c-kit + VEGFR-2 + MSCs to differentiate towards cardiovascular cells and their efficiency of repairing the infarcted myocardium after transplantation. Gene expression profile of the cells was analyzed with RNA-sequencing. Potential of differentiation of the cells was determined after induction. Rat models of myocardial infarction were established by ligation of the left anterior descending coronary artery. The cells were treated with hypoxia and serum deprivation for four hours before transplantation. Improvement of cardiac function and repair of the infarcted myocardium were assessed at four weeks after transplantation. Gene expression profile revealed that c-kit + VEGFR-2 + MSCs expressed most smooth muscle-specific and myocardium-specific genes, while expression of endothelium-specific genes was upregulated significantly. After induction with VEGF or TGF-β for two weeks, the cells expressed CD31 and α-SMA respectively. At three weeks, BMP-2-induced cells expressed cTnT. After transplantation of the cells, cardiac function was improved, scar size of the infarcted myocardium was decreased, and angiogenesis and myocardial regeneration were enhanced significantly. Moreover, paracrine in the myocardium was increased after transplantation. These results suggest that c-kit + VEGFR-2 + MSCs have a potential of differentiation towards cardiovascular cells. Transplantation of c-kit + VEGFR-2 + MSCs is effective for repair of the infarcted myocardium. c-kit + VEGFR-2 + MSCs may be a reliable source for cell therapy of ischaemic diseases. Graphical abstract