Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

Abstract

Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

Therapeutic Potential of “Exosomes Derived Multiple Allogeneic Proteins Paracrine Signaling: Exosomes d-MAPPS” is Based on the Effects of Exosomes, Immunosuppressive and Trophic Factors

“…In addition to the cells of mesodermal origin (osteoblasts, chondroblasts, and adipocytes), MSCs are capable of generating neural cells, hepatocytes, alveolar epithelial cells, insulinproducing cells, cardiomyocytes, indicating their clinical application (7)(8)(9)(10)(11)(12)(13)(14). Several lines of evidence suggested that MSCs have capacity to differentiate into functional cardiomyocytes (9), hepatocytes (10,11), alveolar epithelial cells and lung precursor cells (13) contributing to the regeneration of injured myocardium, liver and lungs (12,(15)(16)(17). Additionally, in paracrine manner, through the production of immunomodulatory factors (indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), nitric oxide (NO), transforming growth factor beta (TGF-β), interleukin (IL)-10, interleukin 1 receptor antagonist (IL-1Ra) and growth related oncogene (GRO), MSCs are able to suppress detrimental autoimmune response and to attenuate autoimmune and chronic, inflammatory diseases (3,18,19).…”

Adjuvant role of macrophages in stem cell-induced cardiac repair in rats

“…The main cells used for stem cell therapy for cardiac regeneration are MSCs, cardiac progenitor cells, and differentiated endothelial cells 17 – 19 . In clinical studies of ischemic heart disease, improvement was shown in the left ventricular ejection fraction in only 8 of 22 trials, and this analysis concluded that adult stem cell therapy was not ready for routine clinical application 20 .…”

Comparison of the Cardiomyogenic Potency of Human Amniotic Fluid and Bone Marrow Mesenchymal Stem Cells

“…The expression of cardiomyogenic differentiation markers cTNT, βMHC and ASA by 5-aza treated cells was analyzed by fluorescent immunocytochemistry. Quantitative analysis of immunoflorescent images revealed that as compared to BM-MSC, AF-MSC had significantly higher expression of cTNT (5.0×10 4 ±0.6×10 4 4 ; p＜0.05) (Fig. 4).…”

“…MSC can also be obtained from fetal tissues such as amniotic fluid, umbilical cord blood and Wharton's jelly (3). Of these, the bone marrow (BM) derived MSC (BM-MSC) have been most commonly studied for myocardial regeneration in several pre-clinical and clinical studies but the therapeutic outcome has been variable, which may be because of their limited cardiomyogenic potential (4)(5)(6). The collection of MSC from BM entails an invasive procedure and it is difficult to get MSC from healthy individuals.…”