title: Dose-dependent effects of intravenous allogeneic mesenchymal stem cells in the infarcted porcine heart.
abstract: Intravenous delivery of mesenchymal stem cells (MSCs) preserves myocardial function after infarction. This dose-escalating study was performed to examine pathologic remodeling and scar formation in a pig model of permanent coronary occlusion without restoration of reperfusion. MSCs labeled with fluorescent dye 48 h or saline (negative control, n = 8) were given intravenously 48 h post proximal left anterior descending artery occlusion. Animals received either autologous or allogeneic MSCs in doses from 1 x 10(3) up to 1 x 10(6) per kg bodyweight from an unrelated donor pig. Infarct size and myocardial function were assessed after 1 month. Morphologic analysis revealed that labeled autologous MSCs migrated in the peri-infarct region resulting in smaller infarct size (19 +/- 7% vs. 32 +/- 7%, p < 0.008) and higher fractional area shortening (33 +/- 7% vs. 21 +/- 3%, p < 0.001). Similarly, allogeneic MSCs had dose-dependent beneficial effects on cardiac function, statistically significant at 1 x 10(5) and 1 x 10(6) cells per kg bodyweight. Autologous as well as allogeneic MSCs specifically "home" to the heart after systemic delivery, leading to limited myocardial infarct size and improved functional outcome, even without coronary reperfusion. Therefore, intravenously administration of MSCs is an attractive minimal-invasive approach for cardiac tissue repair.
authors.affiliation: Department of Cardiology, University of Heidelberg, Koesching, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wolf
authors.forename: Adrian
authors.initials: A
authors.lastname: Reinhard
authors.forename: Anja
authors.initials: A
authors.lastname: Seckinger
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Helmut
authors.initials: H
authors.lastname: Kuecherer
authors.forename: Alexander
authors.initials: A
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001835:Body Weight; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000000981:diagnostic imaging; D005453:Fluorescence; D006334:Heart Function Tests; D006439:Hemodynamics; D007275:Injections, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D009929:Organ Size; D010477:Perfusion; D013552:Swine; D014463:Ultrasonography; D015430:Weight Gain