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European Journal of Heart Failure 2005 7(5):722-729; doi:10.1016/j.ejheart.2005.06.005
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© 2005 European Society of Cardiology

Haematopoietic stem cells improve cardiac function after infarction without permanent cardiac engraftment

Florian P. Limbourga,*,1, Stefanie Ringes-Lichtenberga,1, Arnd Schaefera, Christoph Jacobyb, Yasmin Mehraeinc, Mark D. Jägerd, Anne Limbourga, Martin Fuchsa, Gunnar Kleina, Matthias Ballmaiere, Hans-J. Schlittd, Juergen Schraderb, Denise Hilfiker-Kleinera and Helmut Drexlera

a Department of Cardiology and Angiology, Medizinische Hochschule Hannover Carl Neuberg Str. 1, 30625 Hannover, Germany
b Inst. of Heart and Circulatory Physiology University of Duesseldorf, Germany
c Department of Human Genetics University of Saarland, Homburg, Germany
d Department of Visceral and Transplant Surgery Medizinische Hochscule Hannover, Germany
e Department of Pediatric Hematology and Oncology Medizinische Hochschule Hannover, Germany

* Coresponding author. Tel.: +49 511 532 3270; fax +49 511 532 3263. Email address: limbourg.florian{at}mh-hannover.de


   Abstract

Background: Transplantation of bone marrow derived adult stem cells (BMC) improves cardiac function after acute myocardial infarction (MI). However, the cell population mediating myocardial recovery and the fate of the transplanted cells are still controversial.

Aims: We determined the effects of Sca-1+ c-kit+ lin- haematopoietic BMC on cardiac function after MI and the cell fate after transplantation.

Methods: Sca-1+ c-kit+ lin- BMC of male donor C57BL/6 mice were transplanted by intravenous injection into syngenic females after permanent MI. LV dimensions and function were determined by echocardiography and cardiac magnetic resonance imaging, transplanted BMC were identified by Y chromosome DNA in situ hybridization.

Results: BMC treatment completely prevented LV dilation (LV enddiastolic volume BMC 70±16 µl vs. control 122±41 µl; p <0.05) and improved fractional shortening (BMC 22.9±8% vs. control 15.4±8.4%; p <0.05) and ejection fraction (BMC 68.2±6.6% vs. control 52±14.3%, p <0.05) as early as 3 days after transplantation, but did not decrease infarct size (BMC 27±6% vs. control 28±7%, p =n.s.). After 4 weeks, only sporadic cells of male origin were identified in infarcted hearts (<0.01% of periinfarct cells).

Conclusion: Intravenous injection of sca-1+ c-kit+ lin BMC after MI improves LV dimensions and function without evidence for long term engraftment.

Key Words: Stem cells • Transdifferentiation • Transplantation • Experimental myocardial infarction • Magnetic resonance imaging


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