Cellular Care and Extracellular Vesicles
Therapies of Heart Failure
Department of Internal Medicine, State Medical University for Zaporozhye, Ukraine
Submission: March 16, 2019; Published: May 09, 2019
*Corresponding author: Alexander Berezin, Professor, MD, PhD, Consultant of Therapeutic Unit, Internal Medicine Department, State Medical University for Zaporozhye, 26, Mayakovsky Av., Zaporozhye, Postcode 69035, Ukraine
How to cite this article:Alexander Berezin. Cellular Care and Extracellular Vesicles Therapies of Heart Failure. Curr Trends Biomedical Eng & Biosci.
002 2019; 19(2): 556006. DOI: 10.19080/CTBEB.2019.19.556006
Heart failure (HF) is a major factor contributing to premature death in patients with established cardiovascular (CV) disease. Current cell therapies of HF based on at least two different approaches, in which stem cell transplantation and extracellular vesicles (EV) received from pre-treated cells, were used. Although in HF restoring cardiac function aimed improve survival is target of cell therapy, it is not yet yielded whether isolated EVs from circulating progenitor cells, induced pluripotent stem cells (iPSCs), human embryonic stem cells-derived CV progenitors (hESC-Pg) would be effective translators of reparative signals for cardiac repair. The short communication is depicted the role of different cell strategies in HF. It has emphasized lack of strong evidence of clinical advantages implanted EVs to human cells to iPSCs in HF requires comparison in large clinical trials.
Keywords: Heart failure; Cell therapies; Human stem cells; Human progenitors; Progenitor cell-derived extra vesicles
Heart failure (HF) remains a potent fatal end stage of nature evolution of numerous cardiac diseases with complex and uncertain pathophysiology mechanisms [1,2]. There is evidence that the impaired reparative processes in myocardium affecting cardiac myocytes loss, extracellular matrix remodeling, vasculogenesis, neovascularization, abnormal switch-on of metabolic fetal genes, co-regulation of (pro)-oncogenes, overexpression of oxidative molecules and others could be accompanied with progression of HF regardless of its etiologies [3-5]. Wide range of preclinical and clinical studies depicted the innate molecular pathways of the disease that may be used as therapeutic targets for novel agents recovering reparative capacity of the myocardium in HF [6-8].
Extracellular vesicles (EV) are generally defined as intracellular originated particles shedded from the plasma membrane (micro particles) and released after the fusion of the plasma membranes or formed from endosomes (exosomes) with different size ranges that are usually 100 nm and less . EVs are secreted by numerous cells with different origin due to different signaling mediators and may unleash favorable effects on cardiac reparation by modulation of the metabolism of target cells by transferring signal proteins, growth factors and various genomic materials . EVs acting as cargo of secreted factors are powerful regu lator of cell-to-cell communications. Moreover, EVs are a component of cell secretom that is under direct and indirect influences of various epigenetic factors (pro-inflammatory cytokines, free radicals, micro RNAs, etc.), which co-expressed in HF and are able to change a capability of EVs to repair tissues [4,9]. Indeed, lowered functionality of progenitor cells and weak ability to release EVs with reparative capacity in HF is well established, while the data regarding repair activity of other cells including stem cells, mature cells with different origin are limited . This phenomenon became to be known as progenitor cell dysfunction and it associated with impaired circulating EV immune phenotypes due to imbalance between EVs released form activated and apoptotic precursors . Development and progression of HF strongly associated with elevation of circulating EVs shaping from various populations of the cells including stem cells, progenitor cells and mature endothelial cells, some resident cells, mononuclear cells, adipocytes, cardiac myocytes, that reflects a tenderness of reparative processes and therefore a signature of the EVs may be a marker of severity and prognosis of HF [11,12]. In this context, it is not yet yielded whether isolated EVs from circulating progenitor cells, induced pluripotent stem cells (iPSCs), human embryonic stem cells-derived CV progenitors (hESC-Pg) would be effective translators of reparative signals for cardiac repair
There is evidence in support of cell-based therapies of HF
with stem cells- and progenitor cell-derived EVs could have
promising impact on regeneration of target organs in HF [6,13-
15]. Kervadec et al.  reported that six weeks administration of
EVs released by (hESC-Pg) in post-infarct HF model can provide
equivalent benefits to administered hESC-Pg and hESC-Pg and EV.
Authors revealed that paracrine mechanism might be sufficient
to effect functional recovery of target organs in ischemia-induced
HF during cell-based therapy period. Adamiak et al.  revealed
that iPSC-derived EVs demonstrated sufficient cytoprotective
properties and induced cardiac repair associated with improved
left ventricular function, attenuation of vascularization, and
amelioration of cell apoptosis. There is evidence that the EVs
received from cardiac progenitor cells, but not from fibroblasts,
may improve global cardiac function after injury through
suppression of cell apoptosis . Although an ability of iPSCderived
CV progenitor cells differentiate in to CV lineages in
vitro was found in early animal investigations [17-19], there are
limitations to translate their restoring capabilities (improvement
of myocardial tissue and electrical function) into clinical practice
due to uncertain efficacy in large clinical trials . However, the
cell therapies based on EVs isolation from target cells appears to
be promising. Collectively, all these data confirmed the idea that
the EVs are probably more optimal co-regulator of endogenous
reparative activity of residential cells, neovascularization and
enhancing endothelial function than other transplanted cells
such as iPSCs and endothelial precursors. Finally, whether cell
therapies based on transplantation of iPSCs that may effectively
differentiate into mature cardiac myocytes is superior to EVs
received from pre-treated precursors or stem cells is not fully
clear and requires more investigations in large clinical trials.
In conclusion, there is not strong evidence regarding clinical
advantages of implanted EVs as an active component of the paracrine
secretion by human cells to iPSCs in translation regenerative
medicine in HF. However, the limitations of human iPSCs transplantation
create expectations that EVs received from various
cells could be safer and probably more effective than care based
on pluripotent cell technologies.