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(Circulation. 2003;108:II-253.)
© 2003 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Mesenchymal Progenitor Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Rat Cellular Cardiomyoplasty Model

Siamak Davani, MD; Aliette Marandin, PhD; Nursen Mersin, MD; Bernard Royer, PhD; Bernadette Kantelip, MD, PhD; Patrick Hervé, MD, PhD; Joseph-Philippe Etievent, MD, PhD; Jean-Pierre Kantelip, MD, PhD

From EA-479, Laboratoire de Pharmacologie, Faculté de Médecine, 25000 Besançon, France (S.D., B.R., J.P.K.); INSERM 0119, EA-2284, EFS Bourgogne Franche-Comté, 25000 Besançon, France (A.M., P.H.); EA-479, Service de Chirurgie Thoracique et Cardiovasculaire, CHU Jean Minjoz, 25000 Besançon, France (N.M., J.P.E.); EA-479, Service d’Anatomie Pathologique, CHU Jean Minjoz, 25000 Besançon, France (B.K.). EA-479, Laboratoire de Pharmacologie, Faculté de Médecine, 25000 Besançon, France INSERM 0119, EA-2284, EFS Bourgogne Franche-Comté, 25000 Besançon, France EA-479, Service de Chirurgie Thoracique et Cardiovasculaire, CHU Jean Minjoz, 25000 Besançon, France EA-479, Service d’Anatomie Pathologique, CHU Jean Minjoz, 25000 Besançon, France

Correspondence to Siamak Davani, Laboratoire de Pharmacologie, CHU Jean Minjoz, 25000 Besançon, France. Phone: +33 381 669 226, Fax: +33 381 668 483, E-mail: davani{at}ufc-chu.univ-fcomte.fr

Background— Cellular cardiomyoplasty is a promising approach to improve postinfarcted cardiac function. The differentiation pathways of engrafted mesenchymal progenitor cells (MPCs) and their effects on the left ventricular function in a rat myocardial infarct heart model were analyzed.

Methods and Results— A ligation model of left coronary artery of Lewis rats was used. MPCs were isolated by bone marrow cell adherence. Seven days after ligation, MPCs labeled with 4',6-diamidino-2'-phenylindole were injected into the infarcted myocardium (n=8). Culture medium was injected in the infarcted myocardium of control animals (n=8). Thirty days after implantation, immunofluorescence studies revealed some engrafted cells expressing a smooth muscle phenotype ( SM actin⁺), as similarly observed in culture. Other engrafted cells lost their smooth muscle phenotype and acquired an endothelial phenotype (CD31⁺). Furthermore, vessel density was augmented in the MPC group in comparison with the control group. After 30 days, echocardiography showed an improvement on left ventricular performance in the MPCs compared with the control group.

Conclusions— In vivo administration of syngenic MPCs into a rat model of myocardial infarcted heart was safety demonstrated. Some engrafted cells appeared to differentiate into endothelial cells and loss their smooth muscle phenotype. MPC engraftment might to contribute to the improvement on the cardiac function in such a setting.

Key Words: stem cells • myocardial infarction • transplantation