These authors contributed equally to this work.
Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts
Article first published online: 24 SEP 2007
©2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 12, Issue 2, pages 507–521, April 2008
How to Cite
Penna, C., Raimondo, S., Ronchi, G., Rastaldo, R., Mancardi, D., Cappello, S., Losano, G., Geuna, S. and Pagliaro, P. (2008), Early homing of adult mesenchymal stem cells in normal and infarcted isolated beating hearts. Journal of Cellular and Molecular Medicine, 12: 507–521. doi: 10.1111/j.1582-4934.2007.00121.x
- Issue published online: 24 SEP 2007
- Article first published online: 24 SEP 2007
- Received: June 28, 2007; Accepted: September 5, 2007
- isolated beating heart;
- stem cell homing;
- myocardial injuries;
Little is known on the early homing features of transplanted mesenchymal stem cells (MSCs). We used the isolated rat heart model to study the homing of MSCs injected in the ventricular wall of a beating heart. In this model all types of cells and matrix elements with their interactions are represented, while external interferences by endothelial/neutrophil interaction and neurohormonal factors are excluded. We studied the morphology and marker expression of MSCs implanted in normal hearts and in the border-zone of infarcted myocardium. Early morphological adaptation of MSC homing differs between normal and infarcted hearts over the first 6 hrs after transplantation. In normal hearts, MSCs migrate very early through the interstitial milieu and begin to show morphological changes. Yet, in infarcted hearts MSCs remain in the site of injection forming clusters of round-shaped cells in the border-zone of the infarcted area. Both in normal and infarcted hearts, immuno-histochemistry and confocal imaging showed that, besides the proliferative marker proliferating cell nuclear agent (PCNA), some transplanted cells early express myoblastic maker GATA-4, and some of them show a VWF immunopositivity. Moreover, a few hours after injection connexin-43 is well evident between cardiomy-ocytes and injected cells. This study indicates for the first time that the isolated beating heart is a good model to study early features of MSC homing without external interferences. The results show (i) that MSCs start to change marker expression few hours after injection into a beating heart and (ii) that infarcted myocardium influences transplanted MSC morphology and mobility within the heart.