PMID- 18953051 OWN - NLM STAT- MEDLINE DCOM- 20090202 LR - 20081202 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 29 IP - 23 DP - 2008 Dec TI - Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction. PG - 2851-8 LID - 10.1093/eurheartj/ehn456 [doi] AB - 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. FAU - Korf-Klingebiel, Mortimer AU - Korf-Klingebiel M AD - Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. FAU - Kempf, Tibor AU - Kempf T FAU - Sauer, Thomas AU - Sauer T FAU - Brinkmann, Eva AU - Brinkmann E FAU - Fischer, Philipp AU - Fischer P FAU - Meyer, Gerd P AU - Meyer GP FAU - Ganser, Arnold AU - Ganser A FAU - Drexler, Helmut AU - Drexler H FAU - Wollert, Kai C AU - Wollert KC LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20081025 PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Cytokines) RN - 0 (Intercellular Signaling Peptides and Proteins) SB - IM MH - Animals MH - Bone Marrow Cells/*metabolism MH - Bone Marrow Transplantation/*methods MH - Coronary Vessels/physiology/*surgery MH - Cytokines/administration & dosage/*metabolism MH - Female MH - Humans MH - Intercellular Signaling Peptides and Proteins MH - Male MH - Mice MH - Middle Aged MH - Myocardial Infarction/*therapy MH - Myocytes, Cardiac/metabolism MH - Treatment Outcome EDAT- 2008/10/28 09:00 MHDA- 2009/02/03 09:00 CRDT- 2008/10/28 09:00 PHST- 2008/10/28 09:00 [pubmed] PHST- 2009/02/03 09:00 [medline] PHST- 2008/10/28 09:00 [entrez] AID - ehn456 [pii] AID - 10.1093/eurheartj/ehn456 [doi] PST - ppublish SO - Eur Heart J. 2008 Dec;29(23):2851-8. doi: 10.1093/eurheartj/ehn456. Epub 2008 Oct 25.