title: Transplantation of fetal cardiomyocytes into infarcted rat hearts results in long-term functional improvement.
abstract: Studies have demonstrated the feasibility of transplanting cardiomyocytes after myocardial infarction (MI). However, persistence and effects on left ventricular (LV) function have not been elucidated in long-term studies. Ventricular fetal cardiomyocytes from embryos of both sexes were injected into marginal regions of MI 4 weeks after suture occlusion of the left anterior descending artery in adult female rats. Two and 6 months after transplantation (Tx), engrafted cells were traced by immunohistochemical in situ hybridization for Y chromosomes or bromodeoxyuridine (BrdU) staining, LV dimensions and function were assessed by echocardiography, and LV pressure was assessed ex vivo in a Langendorff perfusion system. Immunohistochemistry for alpha-sarcomeric actin and Y chromosomes revealed the presence of transplanted cells in infarcted host myocardium at both 2 and 6 months. End-diastolic LV diameter markedly decreased after Tx and fractional shortening gradually increased after Tx (31.3 +/- 4.5% before Tx, 45.4 +/- 4.2% at 6 months; p<0.005). Wall area fraction and MI size were unaffected by Tx. In hearts with MI, but not in normal hearts, Tx led to the development of higher pressures (87 +/- 18 versus 38 +/- 8 mmHg, 6 months post-Tx versus nontreated). After catecholamine stimulation, both infarcted and normal hearts developed higher pressures after Tx (p<0.005), ultimately associated with reduced mortality after Tx versus nontreated. Transplanted cardiomyocyte-rich graft cells persist in host myocardium and mediate continuous improvement of LV function and survival in a rat model of MI even during long-term follow-up, possibly involving a catecholamine-sensitive mechanism.
authors.affiliation: Medizinische Klinik I and Department of Molecular Cardiovascular Research, Department of Cardiology, University Hospital Aachen, Aachen, Germany. erik.skobel@t-online.de
authors.forename: Erik
authors.initials: E
authors.lastname: Skobel
authors.forename: Alexander
authors.initials: A
authors.lastname: Schuh
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Schwarz
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Andreas
authors.initials: A
authors.lastname: Franke
authors.forename: Sebastian
authors.initials: S
authors.lastname: Breuer
authors.forename: Kalle
authors.initials: K
authors.lastname: Günther
authors.forename: Thorsten
authors.initials: T
authors.lastname: Reffelmann
authors.forename: Peter
authors.initials: P
authors.lastname: Hanrath
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D005260:Female; D005500:Follow-Up Studies; D008137:Longitudinal Studies; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis* / Q000196:embryology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000196:embryology / Q000209:etiology / Q000601:surgery*