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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial
Hiroshi Kawada1, Jun Fujita, Kentaro Kinjo
1Division of Hematology, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Insights
Bone marrow stem cells contribute to heart repair after myocardial infarction. Mesenchymal stem cells (MSCs) are identified as the primary source of these bone marrow-derived cardiomyocytes.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Bone marrow (BM) cells are known to aid regeneration after myocardial infarction (MI).
- The specific BM cell types responsible for generating new cardiomyocytes remain unidentified.
Purpose of the Study:
- To identify the origin of bone marrow (BM)-derived cardiomyocytes following myocardial infarction (MI).
- To investigate the role of mesenchymal stem cells (MSCs) in cardiac regeneration.
Main Methods:
- Utilized two independent clonal studies involving transplantation of specific BM cell populations (CD34(-)KSL-SP cells and whole BM cells) into irradiated mice.
- Induced myocardial infarction (MI) and administered granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells.
- Transplanted clonally purified, cardiomyogenic (CMG) EGFP-expressing mesenchymal stem cells (MSCs) into irradiated mice, followed by MI induction and G-CSF treatment.
Main Results:
- Transplantation of whole BM cells resulted in over 5000 EGFP(+) actinin(+) cells in the myocardium, while CD34(-)KSL-SP cells yielded only 3 such cells, indicating a non-hematopoietic origin.
- EGFP(+) actinin(+) cells were observed in the ischemic myocardium after transplantation of CMG cells, confirming their differentiation into cardiomyocytes.
- These findings suggest that non-hematopoietic BM cells, specifically MSCs, are the predominant source of BM-derived cardiomyocytes.
Conclusions:
- Mesenchymal stem cells (MSCs) are the primary source of bone marrow (BM)-derived cardiomyocytes.
- These findings elucidate the cellular origin of cardiac regeneration following myocardial infarction (MI).
- Highlights the therapeutic potential of MSCs in treating heart damage.
Abstract:
Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-) c-kit(+)Sca-1(+) lineage(-) side population (CD34(-)KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP(+) actinin(+) cells in myocardium of CD34(-) KSL-SP cells in mice that received transplants, but more than 5000 EGFP(+) actinin(+) cells in whole BM cell in mice that received transplants, suggesting that most of EGFP(+) actinin(+) cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP(+) actinin(+) cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.
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