Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells

Abstract

Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown. Recent studies suggest that transplanted stem cells primarily exert their effects through communicating with endogenous tissues via the release of exosomes containing cardioprotective molecules such as miRNAs, which upon uptake by recipient cells may stimulate survival, proliferation, and angiogenesis. Exosomes are also effective therapeutic agents in isolation and may provide a feasible alternative to stem cell transplantation. We hypothesize that EleS enhances CSC-mediated cardiac repair through its beneficial effects on production of cardioprotective exosomes. Moreover, we hypothesize that the beneficial effects of biventricular pacing in patients with heart failure may in part result from EleS-induced preconditioning of endogenous CSC to promote cardiac repair. With future research, our hypothesis may provide applications to optimize stem cell therapy and augment current pacing protocols, which may significantly advance the treatment of patients with heart disease.

Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA-210 in an nSMase2-dependent way

“…Several approaches have been taken to optimize such therapy by treating donor cell prior to exosome extraction. For example, electroporation or genetic modifications of exosome-producing cells has been used to enhance exosome-mediated therapy through a selective enrichment of secreted factors [10,25–27]. Our results provide evidence for both enhanced therapy and mechanism of action of exosomes by hypoxia.…”

Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects

“…The latter can be explained by the stimulation and production of exosomes that contain cardioprotective molecules (Liu et al, 2012;Matsumoto et al, 2013;Grumbles et al 2013;Huang et al, 2011). In particular, exosomes are useful tools for cell-cell communication in the normal and diseased retina (Campbell et al, 2016;Locke et al, 2014;Atienzar-Aroca et al, 2016) and exert different biological actions depending on their host cell. In fact, it is possible that exosomes may play a critical role in the ES-induced changes in chorioretinal blood flow observed after treatment (Atienzar-Aroca et al, 2016;Wang et al, 2009).…”

Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis

“…Exosomes can carry miRNAs to modify the molecular signals of recipient cells. Therefore, miRNAs play a key role for exosome- mediated communication [11, 37]. Sorting miRNAs into exosomes is cell-specific and related to cytopathophysiology.…”