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

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 dif...

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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
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cited_by cdi_FETCH-LOGICAL-c404t-a6e27d94418a05e471008ed6ef8c0db50d692fd350c17c0da01e470521382b8c3
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container_issue 1
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container_title Stem cell reviews and reports
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creator Zhou, Pei
Yu, Shu-na
Zhang, Hai-feng
Wang, Yong-li
Tao, Ping
Tan, Yu-zhen
Wang, Hai-jie
description 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
doi_str_mv 10.1007/s12015-022-10430-z
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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. 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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</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35962935</pmid><doi>10.1007/s12015-022-10430-z</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-1783-9617</orcidid><oa>free_for_read</oa></addata></record>
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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
title c-kit+VEGFR-2+ Mesenchymal Stem Cells Differentiate into Cardiovascular Cells and Repair Infarcted Myocardium after Transplantation
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