Efficacy and Mode of Action of Mesenchymal Stem Cells in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review

Abstract

Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA.

Cell Therapy for Nonischemic Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…As an example, anthracycline‐induced cardiomyopathy is strongly linked to an increase in cardiac oxidative stress and accumulation of reactive oxygen species leading to endothelial dysfunction and cardiotoxicity 39 . Administration of MSCs can alleviate anthracycline induced oxidative stress and improve endothelial dysfunction 40,41 . Furthermore, a recent study evaluated the role of genetic influences in determining responsiveness to cell therapy in NICM and reported that individuals with certain genetic variants can have greater clinical benefit compared to others 42 .…”

“… 39 Administration of MSCs can alleviate anthracycline induced oxidative stress and improve endothelial dysfunction. 40 , 41 Furthermore, a recent study evaluated the role of genetic influences in determining responsiveness to cell therapy in NICM and reported that individuals with certain genetic variants can have greater clinical benefit compared to others. 42 Taken together, these factors can help individualize the approach to cell therapy in NICM populations to improve responsiveness.…”

Endocardial Endothelial Dysfunction and Unknown Polymorphic Composite Accumulation in Heart Failure

“…Cardiomyopathies are an important and heterogeneous group of diseases that contribute to HF [29]. The main types of primary cardiomyopathy are hypertrophic cardiomyopathy (HCM), DCM, restrictive cardiomyopathy, arrhythmogenic right ventricular dysplasia, and transthyretin amyloid cardiomyopathy [30].…”

Disease-Focused Research Using Stem Cells

“…In addition to GVHD, an increasing number of studies and approximately a thousand MSC clinical trials ramify to most medical specialties, especially cardiovascular medicine, neurology, autoimmune diseases, and musculoskeletal diseases, highlighting that the application potential of MSCs is far from being exhausted [ 6 ]. Therefore, a review covering MSC therapy for nonischemic dilated cardiomyopathy (NIDCM) [ 7 ] and a research article developing MSCs as the next-generation cell-based therapeutics for atopic dermatitis (AD) [ 8 ] are included in this Special Issue.…”

“…Although most clinical trials of MSC therapy on ischemic heart failure have focused on treating the direct myocardial damage with immune-mediated abnormalities underlying nonischemic dilated cardiomyopathy, the fittingness of MSCs to answer both of these issues remained poorly evaluated with scarce numbers of research. Hoeeg et al presented a holistic review on efficacy and the mode of action of MSC therapy in NIDCM encompassing an up-to-date total of 27 studies (clinical and preclinical) with prospective questions and areas in need of further investigation [ 7 ].…”