Heart Cell Transplantation Improves Heart Function in Dilated Cardiomyopathic Hamsters

Abstract

Background-Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium.This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. Methods and Results-Ventricular heart cells were isolated from 4-week-old BIO 53.58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4ϫ10 6 cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, nϭ12 each). Sham-operated hamsters (nϭ12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (PϽ0.001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915Ϯ253 versus control 453Ϯ120 and sham 530Ϯ187 mm Hg/s, PϽ0.001, balloon volume of 15 L). No differences in ventricular function were found between control and sham-operated hamsters. Conclusions-The

Heart Preservation Using Continuous Ex Vivo Perfusion Improves Viability and Functional Recovery

“…A major advantage of the Langendorff model is its ability to specifically address our study aim of directly comparing CP with CS, the current gold standard, without the wide range of confounding effects present in a transplantation model. 33 This method is well-established 19,20,[34][35][36][37] and has a track record of predicting the clinical performance of a wide range of clinical protocols in cardiac surgery, including anti-ischemic interventions 31 and methods of cardiac preservation. 38,39 Although the heart rate and preload…”

Cellular cardiomyoplasty: clinical application

“…The presence of intercalated disks and connexin 43, a marker of gap junctions required for cell to cell electrical coupling, has been experimentally demonstrated within grafted cardiomyocytes and between grafted cells and host myocytes resulting in improved systolic and diastolic ventricular function. In addition to availability, the clinical application of fetal and neonatal cells raises immunologic and ethical questions [23].…”

“…The main mechanisms involved determining the beneficial effects of cellular cardiomyoplasty appear to be: reduction of size and fibrosis of infarct scars, limitation of postischemic ventricular remodeling, improvement of left ventricular wall thickening and compliance (diastolic pressure-strain relationship), and increase in regional myocardial contractility (Table 2) [23], in a canine model of idiopathic dilated cardiomyopathy [15], and in doxorubicin-induced heart failure [33]. On the basis of these experimental results cellular CMP may improve heart function in patients with nonischemic cardiomyopathy.…”

New system for real time study of in vivo migration and differentiation of stem cells

“…Cell therapy appears to be a promising field for the treatment of human diseases. As part of this new field, transplantation of smooth muscle cells has undergone extensive investigation in recent years as a potential therapy, mainly for the repair of aneurysms (Allaire et al 2002), myocardial ischemia (Yoo et al 2000) or for cardiac graft (Ozawa et al 2002). The fetal brain, characterized by active neurogenesis, has been suggested to be a promising source of therapeutic neural stem cells (Flax et al 1998).…”