title: Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model.
abstract: Cell based therapy has been shown to attenuate myocardial dysfunction after myocardial infarction (MI) in different acute and chronic animal models. It has been further shown that stromal-cell derived factor-1α (SDF-1α) facilitates proliferation and migration of endogenous progenitor cells into injured tissue. The aim of the present study was to investigate the role of exogenously applied and endogenously mobilized cells in a regenerative strategy for MI therapy. Lentivirally SDF-1α-infected endothelial progenitor cells (EPCs) were injected after 90 min. of ligation and reperfusion of the left anterior descending artery (LAD) intramyocardial and intracoronary using a new rodent catheter system. Eight weeks after transplantation, echocardiography and isolated heart studies revealed a significant improvement of LV function after intramyocardial application of lentiviral with SDF-1 infected EPCs compared to medium control. Intracoronary application of cells did not lead to significant differences compared to medium injected control hearts. Histology showed a significantly elevated rate of apoptotic cells and augmented proliferation after transplantation of EPCs and EPCs + SDF-1α in infarcted myocardium. In addition, a significant increased density of CD31(+)  vessel structures, a lower collagen content and higher numbers of inflammatory cells after transplantation of SDF-1 transgenic cells were detectable. Intramyocardial application of lentiviral-infected EPCs is associated with a significant improvement of myocardial function after infarction, in contrast to an intracoronary application. Histological results revealed a significant augmentation of neovascularization, lower collagen content, higher numbers of inflammatory cells and remarkable alterations of apoptotic/proliferative processes in infarcted areas after cell transplantation.
authors.affiliation: Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, RWTH Aachen University, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schuh
authors.forename: Andreas
authors.initials: A
authors.lastname: Kroh
authors.forename: Simone
authors.initials: S
authors.lastname: Konschalla
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Radoslav M
authors.initials: RM
authors.lastname: Sobota
authors.forename: Erik Al
authors.initials: EA
authors.lastname: Biessen
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
authors.forename: Tolga Taha
authors.initials: TT
authors.lastname: Sönmez
authors.forename: Sönmez
authors.initials: S
authors.lastname: Tolga Taha
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Alexander
authors.initials: A
authors.lastname: Sasse
mesh_terms: D000818:Animals; D017209:Apoptosis; D006328:Cardiac Catheterization / Q000379:methods; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004452:Echocardiography; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000473:pathology; D016086:Lentivirus; D023421:Models, Animal; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D003094:Collagen