Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: Advances and Challenges

Abstract

Ischemic heart disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect, manipulating their cardiomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June, 2018.

Cardiomyocyte Death and Genome-Edited Stem Cell Therapy for Ischemic Heart Disease

“…The major benefit of MSC therapy is derived from the paracrine effects. The MSC secretome has cardiovascular protection effects and is known to modulate the death of residue cells caused by the pathological environment [17,76]. Nevertheless, even though MSCs show sufficient therapeutic potential in regeneration of damaged cardiomyocytes and ischemic heart diseases, there are still obvious limitations that should be overcome, including an incomplete understanding of the therapeutic mechanism, and low settlement and survival rates of the transplanted cells [79].…”

“…The therapeutic effects of stem cell therapy in cardiovascular disease has been demonstrated not only in the various studies, but also in preclinical models where positive results have been reported [2,83]. However, there are apparent limitations that still need to be solved in order to utilize stem cell therapy in patients with cardiovascular disease [17]. In this regard, the introduction of additional genes reinforces the function of stem cells while still retaining the advantages of existing stem cell therapy.…”

“…In this regard, stem cell therapy has received much attention and numerous studies related to it have been conducted. Diverse stem cells, including pluripotent stem cells, tissuederived mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs) have been tested in preclinical experimental models [14][15][16][17][18]. Each of these cells have been confirmed to have effects such as protection of cardiomyocytes, acceleration of angiogenesis and support of heart tissue repair through paracrine effects.…”

Growth Factor Screening in Dystrophic Muscles Reveals PDGFB/PDGFRB-Mediated Migration of Interstitial Stem Cells

“…Cardiac interstitial cells, such as cardiac mesoangioblasts [11], are an appealing cell therapy source because of their beneficial paracrine effects on cardiac remodelling [12]. However, when injected directly into the myocardium or skeletal muscles, stem cells show very limited migration potential.…”

Wnt11 preserves mitochondrial membrane potential and protects cardiomyocytes against hypoxia through paracrine signaling

“…Bone marrow–derived mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes (CMs) . Soluble paracrine factors, secreted by MSCs injected into animal models of cardiovascular disease, conferred cardioprotection by inducing neovascularization and regeneration . These soluble MSC paracrine factors can be produced by genetically engineered stem cells …”