Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide. According to the World Health Organization (WHO), an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty) is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs) in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.

New Frontiers in Regenerative Medicine in Cardiology: The Potential of Wharton’s Jelly Mesenchymal Stem Cells

“…As reviewed by Elnakish and colleagues, the use of MSCs in preclinical trials (especially in experimental animal models) showed an improvement of left ventricular function, a decreased size of infarcted area, and a decreased mortality [48]. Nevertheless, bone marrow (BM) and adipose tissue (AT) were extensively studied and still remain the major sources of adult stem cells used in most clinical trials, since their transplantation seems to be related to an improvement of heart physiology [49][50][51][52][53].…”

Evaluation of Sericin as a Fetal Bovine Serum-Replacing Cryoprotectant During Freezing of Human Mesenchymal Stromal Cells and Human Osteoblast-Like Cells

“…Approximately 300 clinical trials utilizing hMSCs have been completed or are in progress. These clinical trials are focused on the treatment of various clinical entities such as bone and connective tissue diseases and injuries, 10 cardiovascular disorders, 11 and autoimmune diseases, 12 including graft versus host reactions 13 (http://www.clinicaltrials.gov, 9.1.2014, keyword ''mesenchymal stem cells'').…”

Neural Crest Stem Cells Can Differentiate to a Cardiomyogenic Lineage with an Ability to Contract in Response to Pulsed Infrared Stimulation

“…Both contraction and relaxation are of larger magnitude on the periphery of the aggregate and close to the optical fiber. Images represent sample PIV results of aggregates before contraction (1), during contraction (2), during relaxation (3), and immediately after relaxation (4). IR, infrared radiation; PIV, particle image velocimetry.…”

“…3 Within the last 20 years, however, cellular cardiomyoplasty has emerged as a potential therapy to help reverse myocardial damage that occurs as a result of an infarction. 4 These therapies apply the perfusion of stem or progenitor cells following an MI in an effort to repopulate the myocardium with functional myocytes. Clinically, patients receiving perfusions of these cells showed modest improvement in cardiac functional parameters, such as increased ejection fraction and decreased end-systolic volume.…”

“…4 MSCs rapidly progressed through small and large animal preclinical models, and transplantation of MSCs showed gains in cardiac function following an MI; however, these results have been largely attributed to paracrine mechanisms as transplanted cells show low survival, engraftment, and differentiation in the host myocardium. 6 The plasticity of MSCs toward a cardiomyogenic lineage has been debated in the literature, with several groups reporting the ability of MSCs to transdifferentiate into cardiomyocytelike cells that exhibit a phenotype of cardiomyocytes, but fail to contract as functional cardiomyocytes.…”