BioMed Central Page 1 of 11 (page number not for citation purposes) Fibrogenesis & Tissue Repair Open Access Research Transplantation of genetically engineered cardiac fibroblasts producing recombinant human erythropoietin to repair the infarcted myocardium Emil Ruvinov 1 , Orna Sharabani-Yosef 1 , Arnon Nagler 2 , Tom Einbinder 3 , Micha S Feinberg 1 , Radka Holbova 1 , Amos Douvdevani 3 and Jonathan Leor* 1 Address: 1 Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel, 2 Institute of Hematology, Sheba Medical Center, Tel-Hashomer, Israel and 3 Department of Nephrology, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, Israel Email: Emil Ruvinov - emilr78@gmail.com; Orna Sharabani-Yosef - ornashy@yahoo.com; Arnon Nagler - a.nagler@sheba.health.gov.il; Tom Einbinder - etom@bezeqint.net; Micha S Feinberg - micha.feinberg@sheba.health.gov.il; Radka Holbova - rholbova@yahoo.co.uk; Amos Douvdevani - amosd@bgu.ac.il; Jonathan Leor* - leorj@post.tau.ac.il * Corresponding author Abstract Background: Erythropoietin possesses cellular protection properties. The aim of the present study was to test the hypothesis that in situ expression of recombinant human erythropoietin (rhEPO) would improve tissue repair in rat after myocardial infarction (MI). Methods and results: RhEPO-producing cardiac fibroblasts were generated ex vivo by transduction with retroviral vector. The anti-apoptotic effect of rhEPO-producing fibroblasts was evaluated by co-culture with rat neonatal cardiomyocytes exposed to H 2 O 2 -induced oxidative stress. Annexin V/PI assay and DAPI staining showed that compared with control, rhEPO forced expression markedly attenuated apoptosis and improved survival of cultured cardiomyocytes. To test the effect of rhEPO on the infarcted myocardium, Sprague-Dawley rats were subjected to permanent coronary artery occlusion, and rhEPO-producing fibroblasts, non-transduced fibroblasts, or saline, were injected into the scar tissue seven days after infarction. One month later, immunostaining identified rhEPO expression in the implanted engineered cells but not in controls. Compared with non-transduced fibroblasts or saline injection, implanted rhEPO-producing fibroblasts promoted vascularization in the scar, and prevented cell apoptosis. By two-dimensional echocardiography and postmortem morphometry, transplanted EPO-engineered fibroblasts did not prevent left ventricular (LV) dysfunction and adverse LV remodeling 5 and 9 weeks after MI. Conclusion: In situ expression of rhEPO enhances vascularization and reduces cell apoptosis in the infarcted myocardium. However, local EPO therapy is insufficient for functional improvement after MI in rat. Published: 3 November 2008 Fibrogenesis & Tissue Repair 2008, 1:7 doi:10.1186/1755-1536-1-7 Received: 9 March 2008 Accepted: 3 November 2008 This article is available from: http://www.fibrogenesis.com/content/1/1/7 © 2008 Ruvinov et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.