Heart Failure Stem Cells Induced to Cardiomyocytes
(HealthDay News) – Human-induced pluripotent stem cells (hiPSCs) derived from patients with heart failure can be induced to differentiate into cardiomyocytes (CMs), which then can integrate with host cardiac tissue.
Limor Zwi-Dantsis, from the Technion-Israel Institute of Technology in Haifa, and colleagues reprogrammed dermal fibroblasts from two patients with heart failure by retroviral delivery of Oct4, Sox2, and Klf4 or by use of an excisable polycistronic lentiviral vector. The resulting heart failure-HiPSCs were then induced to differentiate into CMs.
The investigators found that the heart failure-hiPSCs differentiated into cardiomyocytes with efficiency comparable to control hiPSCs. The cardiomyocyte phenotype of the differentiating heart failure-hiPSC-cardiomyocytes (hiPSC-CMs) was confirmed in gene expression and immunostaining studies. The development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation were demonstrated on multi-electrode array recordings. In co-culture studies, functional integration and synchronized electrical activities were observed between hiPSC-CMs and neonatal rat cardiomyocytes. The heart failure-hiPSC-CMs were able to engraft, survive, and structurally integrate with host cardiomyocytes in in vivo transplantation studies in the rat heart.
"In this study, we demonstrated that heart failure-hiPSC-CMs can survive following transplantation, form stable cell grafts, and establish electromechanical junctions with host cardiomyocytes in the healthy rat heart," the authors write. "Future studies will have to evaluate whether similar engraftment could also occur in small and large animal models of cardiac injury and whether such an engraftment could lead to a functional benefit."
The study was partially funded by the Johnson & Johnson Technion research grant.