title: Repetitive transplantation of different cell types sequentially improves heart function after infarction.
abstract: Cell-based therapy is considered a novel and potentially new strategy in regenerative medicine. But the efficacy of cell-based therapy has been limited by the poor survival of the transplanted cells in an ischaemic environment. The goal of the present study is to present a possibility to increase survival of the transplanted cardiomyocytes, by increasing the vascularization of the infarcted area. First, we injected endothelial progenitor cells (EPCs) to augment the vascular density in infarcted areas and to improve the benefit of a subsequent Tx of foetal cardiomyocytes. Serial echocardiography indeed showed significant improvement of the left ventricular function after application of EPC and a significant additive improvement after Tx of foetal cardiomyocytes. In contrast, repetitive EPC transplantation as a control group did not show an additional improvement after the second transplantation. Histologically, cells could be readily detected after Tx by BrdU-staining for EPC and by carboxy-fluorescein diacetate succinimidyl ester (CFSE)-staining for foetal cardiomyocytes. Staining for CD31 revealed a significant increase in vessel density in the infarction area compared with medium controls, possibly contributing to the benefit of transplanted foetal cardiomyocytes. Notably, a significant increase in the number of apoptotic cells was observed in cell-transplanted hearts accompanied by an increase in proliferation, collagen content and neutrophil infiltration, suggesting an active remodelling concomitant with sustained inflammatory processes. In conclusion, repetitive Tx of different cell types after myocardial infarction in rat hearts significantly improved left ventricular function and could represent a feasible option to enhance the benefit of cell therapy.
authors: Department of Cardiology, Pulmonology, Angiology and Internal Medicine Intensive Care, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Schuh
authors: S
authors: Alexander
authors: Alexander
authors: A
authors: Sasse
authors: Simone
authors: S
authors: Konschalla
authors: Andreas
authors: A
authors: Kroh
authors: Marc W
authors: MW
authors: Merx
authors: Christian
authors: C
authors: Weber
authors: Elisa A
authors: EA
authors: Liehn
mesh_terms: D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004452:Echocardiography; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D005240:Feasibility Studies; D005260:Female; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism; D016277:Ventricular Function, Left