Generation, Characterization, and Potential Therapeutic Applications of Cardiomyocytes from Various Stem Cells

Abstract

Heart failure is one of the leading causes of death worldwide. Myocardial cell transplantation emerges as a novel therapeutic strategy for heart failure, but this approach has been hampered by severe shortage of human cardiomyocytes. We have recently induced mouse embryonic stem cells to differentiate into embryoid bodies and eventually, cardiomyocytes. Here, we address recent advancements in cardiomyocyte differentiation from cardiac stem cells and pluripotent stem cells. We highlight the methodologies, using growth factors, endoderm-like cell cocultures, small molecules, and biomaterials, in directing the differentiation of pluripotent stem cells into cardiomyocytes. The characterization and identification of pluripotent stem cell-derived cardiomyocytes by morphological, phenotypic, and functional features are also discussed. Notably, increasing evidence demonstrates that cardiomyocytes may be generated from the stem cells of several tissues outside the cardiovascular system, including skeletal muscles, bone marrow, testes, placenta, amniotic fluid, and adipose tissues. We further address the potential applications of cardiomyocytes derived from various kinds of stem cells. The differentiation of stem cells into functional cardiomyocytes, especially from an extra-cardiac stem cell source, would circumvent the scarcity of heart donors and human cardiomyocytes, and, most importantly, it would offer an ideal and promising cardiomyocyte source for cell therapy and tissue engineering in treating heart failure.

Allogenicity of Human Cardiac Stem/Progenitor Cells Orchestrated by Programmed Death Ligand 1

“…These results indicate that both the initially (Online Figure I) and the cryopreserved investigated cells exhibit phenotypic traits typified by multiple types of previously reported human heart-derived stem/progenitor cell populations. 8,27 Thus, they present a population of CPC with a mixed stem cell phenotype and will be referred to as hCPC throughout the text.…”

“…6,7 Currently, several different populations of CPC are being put forward as potential cell therapies to achieve cardiac repair/regeneration. 8 Clinical applications of autologous human CPC from the Stem Cell Infusion in Patients with Cardiomyopathy (SCIPIO) trial, which uses autologous c-kit-positive cells, and from the CardiosphereDerived Autologous Stem Cells to Reverse Ventricular Dysfunction (CADUCEUS) trial, which uses autologous cardiosphere-derived cells, provide evidence of feasibility and early hints of efficacy in a clinically meaningful setting. 2,9 However, autologous approaches have their limitations, including a lack of therapeutic activity of CPC from the elderly and then typically disease-affected patient population, as well as logistical, economic, and time constraints.…”

Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing

“…These include: (i) delivery of factors aimed at stimulating the repairing ability of resident cardiac stem cells; (ii) reprogramming non-muscle cells (e.g. fibroblasts) into CMs; (iii) identification, manipulation and implantation of stem or progenitor cells [5][6][7]. Although these strategies are promising, they do not achieve cardiac regeneration sufficient to restore function of a failing heart and are still far from replacing classical non-resolutive strategies (rational use of drugs and heart transplantation) [8].…”

“…Observation that mesenchymal stem cells (MSCs) of both homo-and hetero-topic origins can differentiate in-vitro towards cardiac lineage [6,[9][10][11] provoked increasing interest and perspective about the possibility to restore damaged myocardium with MSCs. Since cells "implanted in" or "delivered to" the target site may frequently vanish within few days, some Authors support the hypothesis that MSCs promote positive actions in terms of cardiac functionality due to production of trophic factors, induction of vasculogenesis, and differentiation into CM [5,6].…”

Application of Multi Slice Spiral CT Combined with Head and Neck Digital Subtraction Angiography in the Diagnosis of Head and Neck Vascular Diseases

“…Ischemic stroke is a common cerebrovascular disease, which accounts for 60% to 80% of all cerebrovascular diseases [6]. This study shows that 128 slice spiral CT digital subtraction angiography has high success rate, noninvasive, rapid, simple, high security, and through VR, MIP, MPR and CPR DSCTA postprocessing technology can clearly show the head and neck stenosis plaque location, scope, nature and the degree of stenosis and combined with the original axial images comprehensive analysis of diagnostic accuracy, can provide important reference information for clinical diagnosis and treatment of patients, and a large number of domestic reported DSCTA results can accurately reflect the degree of vascular stenosis [7].…”