Differentiation and migration of Sca1+/CD31− cardiac side population cells in a murine myocardial ischemic model

Liang, Simon X.; Tan, Terence Y.L.; Gaudry, Leonie; Chong, Beng

doi:10.1016/j.ijcard.2008.08.032

« Previous Next »International Journal of Cardiology
Volume 138, Issue 1 , Pages 40-49, 7 January 2010

Differentiation and migration of Sca1+/CD31− cardiac side population cells in a murine myocardial ischemic model

Simon X. Liang
- Center for Vascular Research, Department of Medicine and Hematology, St George Hospital, St George Clinical School, University of New South Wales, Sydney, 2052, Australia
- These authors contributed equally to this publication.
Terence Y.L. Tan
- Center for Vascular Research, Department of Medicine and Hematology, St George Hospital, St George Clinical School, University of New South Wales, Sydney, 2052, Australia
- These authors contributed equally to this publication.
Leonie Gaudry
- Centre for Vascular Research, Department of Hematology, The Prince of Wales Hospital, University of New South Wales, Sydney, Australia
Beng Chong
- Center for Vascular Research, Department of Medicine and Hematology, St George Hospital, St George Clinical School, University of New South Wales, Sydney, 2052, Australia
- Corresponding author. Tel.: +61 2 91132010; fax: +61 2 91133998.

Received 9 December 2007; received in revised form 10 June 2008; accepted 8 August 2008. published online 03 March 2009.

Abstract

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-1α/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-1α 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-1α 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-1α/CXCR4 system might play an important role in the migration of these cells.

Keywords: Stem cells, Side population cells, Myocardial ischemia, Migration, SDF-1α/CXCR4