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European Heart Journal Advance Access originally published online on October 25, 2008
European Heart Journal 2008 29(23):2851-2858; doi:10.1093/eurheartj/ehn456
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction

Mortimer Korf-Klingebiel1, Tibor Kempf1, Thomas Sauer1, Eva Brinkmann1, Philipp Fischer1, Gerd P. Meyer1, Arnold Ganser2, Helmut Drexler1 and Kai C. Wollert1,*

1 Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2 Department of Haematology, Haemostaseology, Oncology, and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany

Received 10 July 2008; revised 10 September 2008; accepted 18 September 2008; online publish-ahead-of-print 25 October 2008.

* Corresponding author. Tel: +49 511 532 4055, Fax: +49 511 532 5307, Email: wollert.kai{at}mh-hannover.de

Aims: Results from clinical trials suggest that cardiac function after acute myocardial infarction (AMI) can be enhanced by an intracoronary infusion of autologous unselected nucleated bone marrow cells (BMCs). Release of paracrine factors has been proposed as a mechanism for these therapeutic effects; however, this hypothesis has not been tested in humans.

Methods and results: BMCs and peripheral blood leucocytes (PBLs) were obtained from 15 patients with AMI and cultured in serum-free medium to obtain conditioned supernatants (SN). BMC-SN stimulated human coronary artery endothelial cell proliferation, migration, and tube formation, and induced cell sprouting in a mouse aortic ring assay. Moreover, BMC-SN protected rat cardiomyocytes from cell death induced by simulated ischaemia or ischaemia followed by reperfusion. While PBL-SN promoted similar effects on endothelial cells and cardiomyocytes, BMC-SN and PBL-SN in combination promoted synergistic effects. As shown by ProteinChip and GeneChip array analyses (each performed in triplicate), BMCs and PBLs expressed distinct patterns of pro-angiogenic and cytoprotective secreted factors.

Conclusion: Our data support the paracrine hypothesis and suggest that characterization of the BMC secretome may lead to an identification of factors with therapeutic potential after AMI.

Key Words: Acute myocardial infarction • Cell therapy • Paracrine hypothesis


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