Cardiac Stem Cell Biology

Human Stem Cells for Modeling Heart Disease and for Drug Discovery

“…c-Kit + hematopoietic stem cells do reside within the bone marrow as well as the heart but have been shown to represent a more committed cell population (7). Nevertheless, the bone marrow hosts a plethora of multipotent adult stem cells, including side population cells, mesenchymal stem cells, and mononuclear stem cells, all of which are being investigated as potential cellular therapies for cardiac regeneration (8) [see Review by Lin and Pu (9)]. CD34 + cells from human peripheral blood, CD31 + circulating endothelial progenitor cells, and adipose-derived stem cells have also demonstrated cardiac regeneration abilities.…”

“…Clinical trials for treatment of post-infarct patients using multipotent adult stem cells are ongoing but with mixed results for their short-term efficacy (8), and there are no current reports about their long-term efficacy. A common drawback has been the poor survival of implanted cells, irrespective of the delivery route, immunosuppression strategy, or timing.…”

“…Autologous or allogeneic adult stem cells— including mesenchymal stem cells, cardiac stem cells, hematopoietic stem cells, mononuclear cells, adipose-derived stem cells, and cardiosphere derived cells—have provided exciting avenues for promoting heart tissue repair (8). Several labs worldwide have also joined the race to demonstrate in vivo transplantation of PSC-CMs in preclinical models that will eventually lead to phase 1 clinical trials.…”

Induced Pluripotent Stem Cells for Cardiovascular Disease: From Product-Focused Disease Modeling to Process-Focused Disease Discovery

“…Importantly, the proliferative nature of iPS cells provides an essentially unlimited pool of patient-specific cardiac progenitors and cardiomyocytes for investigation. Pharmacologic screens for novel therapeutic agents can now be conducted on functional human cardiomyocytes to serve as an individualized read-out of small molecule efficacy without risk of toxicity to the patient [19]. Here, we review the current progress in cardiac disease modeling applications and the future possibilities of cardiovascular disease discovery with patient-specific iPS cells.…”

Cardiovascular regenerative therapeutics via synthetic paracrine factor modified mRNA

“…Nevertheless, given the shortage of donor hearts for transplantation, there is an urgent need for novel therapies to repair severely diseased hearts. To address this issue, there is a growing interest in three research areas for heart regeneration including the use pluripotent stem cells (PSCs) for cell replacement therapy (for a review, see Addis and Epstein, 2013;Lui et al, 2012;Matsa et al, 2014;Vunjak-Novakovic et al, 2011;Xu et al, 2012), direct reprogramming of cardiac fibroblasts into myocardium in vivo (Fu et al, 2013;Ieda et al, 2010;Qian et al, 2012), or replication and reactivation of endogenous quiescent cardiovascular progenitor cells for differentiating into functional blood vessels and de novo cardiac muscle (Chong et al, 2011;Smart et al, 2011;Zangi et al, 2013). In this review, we focus on reactivation of our endogenous regenerative capacity through paracrine mechanisms, and describe a new technological platform via synthetic modified mRNAs to express these factors in vivo in the heart following myocardial infarction.…”