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Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Differentiation and migration of Sca1+/CD31- cardiac side population cells in a murine myocardial ischemic model
Simon X Liang1, Terence Y L Tan, Leonie Gaudry
1Center for Vascular Research, Department of Medicine and Hematology, St George Hospital, St George Clinical School, University of New South Wales, Sydney, 2052, Australia.
Insights
Cardiac side population cells migrate to damaged heart tissue and differentiate into new heart and blood vessel cells after injury. The SDF-1alpha/CXCR4 system aids this cell migration process in vivo.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- Adult heart contains rare Sca1+/CD31- cardiac side population cells with stem/progenitor activity.
- These cells show potential for cardiomyocyte differentiation in vitro.
- In vivo response to myocardial injury is not well understood.
Purpose of the Study:
- Investigate the in vivo behavior of Sca1+/CD31- cardiac side population cells after myocardial infarction.
- Determine their differentiation and migration potential.
- Explore the role of the SDF-1alpha/CXCR4 axis.
Main Methods:
- Isolation of Sca1+/CD31- cardiac side population cells from mouse hearts via FACS.
- Intramyocardial injection into infarcted mouse hearts.
- Immunohistochemistry, migration assays, and analysis of SDF-1alpha/CXCR4 expression.
Main Results:
- Transplanted cells expressed cardiomyocyte and endothelial markers.
- Cells migrated to damaged myocardium after infarction.
- SDF-1alpha and CXCR4 were upregulated in damaged tissue and on cells, respectively.
- SDF-1alpha induced cell migration in vitro.
Conclusions:
- Sca1+/CD31- cardiac side population cells migrate to injured heart areas and differentiate into cardiomyocyte- and endothelial-like cells.
- The SDF-1alpha/CXCR4 system is implicated in mediating this cell migration following ischemic injury.
Background:
Side population cells are a rare subset of cells found in the adult heart that are highly enriched for stem and progenitor cell activity. Recent studies have suggested that Sca1+/CD31- cardiac side population cells are capable of differentiation into cardiomyocytes in vitro. However, the response of these cells to myocardial injury remains unknown in vivo.
Methods:
Sca1+/CD31- cardiac side population cells were isolated from mouse (C57BL6/J) hearts by FACS. These cells were labeled and delivered via an intramyocardial injection into an infracted mouse heart. The differentiation potential of these cells was determined by immunohistochemistry two weeks later. We further tested the migration potential and the relationship of SDF-1alpha/CXCR4 to these cells.
Results:
The transplanted cells were found to express cardiomyocyte or endothelial cell specific markers. Furthermore, when these cells were transplanted into non-infarct myocardium after myocardial infarction, they were found in the damaged myocardium. Consistent with their homing property, we found that SDF-1alpha and CXCR4 were up-regulated in the damaged myocardium and on Sca1+/CD31- cardiac side population cells respectively following myocardial infarction. We also show that SDF-1alpha induced migration of Sca1+/CD31- cardiac side population cells in vitro.
Conclusions:
Our results have suggested that Sca1+/CD31- cardiac side population cells are able to migrate into damaged myocardium from non-ischemic area of the heart and differentiate into both cardiomyocyte- and endothelial-like cells following acute ischemic injury. The SDF-1alpha/CXCR4 system might play an important role in the migration of these cells.

