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Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium

Smits, A.J.M. and Laake van, L.W. and Ouden den, K. and Schreurs, C. and Szuhai, K. and Echteld van, C. J. and Mummery, C.L. and Doevendans, P.A. and Goumans, M.J. (2009) Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium. Cardiovascular Research, 83, 527-35. ISSN 1755-3245.

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AIMS: Recent clinical studies revealed that positive results of cell transplantation on cardiac function are limited to the short- and mid-term restoration phase following myocardial infarction (MI), emphasizing the need for long-term follow-up. These transient effects may depend on the transplanted cell-type or its differentiation state. We have identified a population of cardiomyocyte progenitor cells (CMPCs) capable of differentiating efficiently into beating cardiomyocytes, endothelial cells, and smooth muscle cells in vitro. We investigated whether CMPCs or pre-differentiated CMPC-derived cardiomyocytes (CMPC-CM) are able to restore the injured myocardium after MI in mice. METHODS AND RESULTS: MI was induced in immunodeficient mice and was followed by intra-myocardial injection of CMPCs, CMPC-CM, or vehicle. Cardiac function was measured longitudinally up to 3 months post-MI using 9.4 Tesla magnetic resonance imaging. The fate of the human cells was determined by immunohistochemistry. Transplantation of CMPCs or CMPC-CM resulted in a higher ejection fraction and reduced the extent of left ventricular remodelling up to 3 months after MI when compared with vehicle-injected animals. CMPCs and CMPC-CM generated new cardiac tissue consisting of human cardiomyocytes and blood vessels. Fusion of human nuclei with murine nuclei was not observed. CONCLUSION: CMPCs differentiated into the same cell types in situ as can be obtained in vitro. This excludes the need for in vitro pre-differentiation, making CMPCs a promising source for (autologous) cell-based therapy.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:6996
Deposited On:25 Jan 2010 01:00
Last Modified:13 Oct 2010 12:51

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