Concise Review: Mesenchymal Stem Cells in Cardiovascular Regeneration: Emerging Research Directions and Clinical Applications (original) (raw)
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Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics
Circulation Research, 2004
Mesenchymal stem cells (MSCs) represent a stem cell population present in adult tissues that can be isolated, expanded in culture, and characterized in vitro and in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes, and they can support hematopoietic stem cells or embryonic stem cells in culture. Evidence suggests MSCs can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. When introduced into the infarcted heart, MSCs prevent deleterious remodeling and improve recovery, although further understanding of MSC differentiation in the cardiac scar tissue is still needed. MSCs have been injected directly into the infarct, or they have been administered intravenously and seen to home to the site of injury. Examination of the interaction of allogeneic MSCs with cells of the immune system indicates little rejection by T cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the shelf" therapeutic use for multiple recipients. Clinical use of cultured human MSCs (hMSCs) has begun for cancer patients, and recipients have received autologous or allogeneic MSCs. Research continues to support the desirable traits of MSCs for development of cellular therapeutics for many tissues, including the cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide an excellent model for development of stem cell therapeutics, and their potential use in the cardiovascular system is currently under investigation in the laboratory and clinical settings. (Circ Res. 2004;95:9-20.)
Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality
Stem Cells International, 2012
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.
PloS one, 2011
The possible different therapeutic efficacy of human mesenchymal stem cells (hMSC) derived from umbilical cord blood (CB), adipose tissue (AT) or bone marrow (BM) for the treatment of myocardial infarction (MI) remains unexplored. This study was to assess the regenerative potential of hMSC from different origins and to evaluate the role of CD105 in cardiac regeneration. Male SCID mice underwent LAD-ligation and received the respective cell type (400.000/per animal) intramyocardially. Six weeks post infarction, cardiac catheterization showed significant preservation of left ventricular functions in BM and CD105(+)-CB treated groups compared to CB and nontreated MI group (MI-C). Cell survival analyzed by quantitative real time PCR for human GAPDH and capillary density measured by immunostaining showed consistent results. Furthermore, cardiac remodeling can be significantly attenuated by BM-hMSC compared to MI-C. Under hypoxic conditions in vitro, remarkably increased extracellular aci...
Therapeutic efficacy of mesenchymal stem cells for cardiovascular diseases
Journal of Mind and Medical Sciences, 2021
Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy of CVDs. In particular, we analyze the biological properties of MSCs, elucidate recent clinical findings and clinical trial phases of investigation, highlight clinical therapeutic effects of MSCs, and discuss challenges towards the clinical use of these cells in the therapy of CVDs.
Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges
Molecular Therapy
Cardiac cell-based therapies aim to overcome the limitations of gene therapy via the adoptive transfer of healthy cells, rather than isolated genes. Cells are thought to operate either directly, by replacing the unhealthy cells in the damaged tissue, or indirectly, via the secretion of molecules and microvesicles that stimulate endogenous mechanisms of immune regulation and cardiac regeneration. The cell grafts are derived from adult tissues, such as bone marrow, 17,18 skeletal muscle, 19 and the heart itself 20,21 or from pluripotent stem cells 22,23 , and they may be autologous 17 or allogeneic 18,24 in origin. However, as with gene therapy, cell therapy faces many challenges toward clinical translation. For example, contrary to the original hypothesis that
Mesenchymal Stem Cells for Cardiac Therapy: Practical Challenges and Potential Mechanisms
Stem Cell Reviews and Reports, 2013
Cell based treatments for myocardial infarction have demonstrated efficacy in the laboratory and in phase I clinical trials, but the understanding of such therapies remains incomplete. Mesenchymal stem cells (MSCs) are classically defined as maintaining the ability to generate mesenchyme-derived cell types, namely adipocytes, chondrocytes and osteocytes. Recent evidence suggests these cells may in fact harbor much greater potency than originally realized, as several groups have found that MSCs can form cardiac lineage cells in vitro. Additionally, experimental coculture of MSCs with cardiomyocytes appears to improve contractile function of the latter. Bolstered by such findings, several clinical trials have begun to test MSC transplantation for improving post-infarct cardiac function in human patients. The results of these trials have been mixed, underscoring the need to develop a deeper understanding of the underlying stem cell biology. To help synthesize the breadth of studies on the topic, this paper discusses current challenges in the field of MSC cellular therapies for cardiac repair, including methods of cell delivery and the identification of molecular markers that accurately specify the therapeutically relevant mesenchymal cell types. The various possible mechanisms of MSC mediated cardiac improvement, including somatic reprogramming, transdifferentiation, paracrine signaling, and direct electrophysiological coupling are also reviewed. Finally, we consider the traditional cell culture microenvironment, and the promise of cardiac tissue engineering to provide biomimetic in vitro model systems to more faithfully investigate MSC biology, helping to safely and effectively translate exciting discoveries in the laboratory to meaningful therapies in the clinic.
Korean Circulation Journal, 2021
Mesenchymal stem cells (MSCs) represent a population of adult stem cells residing in many tissues, mainly bone marrow, adipose tissue, and umbilical cord. Due to the safety and availability of standard procedures and protocols for isolation, culturing, and characterization of these cells, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative therapy. Once transplanted into a damaged heart, MSCs release paracrine factors that nurture the injured area, prevent further adverse cardiac remodeling, and mediate tissue repair along with vasculature. Numerous preclinical studies applying MSCs have provided significant benefits following myocardial infarction. Despite promising results from preclinical studies using animal models, MSCs are not up to the mark for human clinical trials. As a result, various approaches have been considered to promote the therapeutic potency of MSCs, such as genetic engineering, physical treatments, growth factor, and pharmacological agents. Each strategy has targeted one or multi-potentials of MSCs. In this review, we will describe diverse approaches that have been developed to promote the therapeutic potential of MSCs for cardiac regenerative therapy. Particularly, we will discuss major characteristics of individual strategy to enhance therapeutic efficacy of MSCs including scientific principles, advantages, limitations, and improving factors. This article also will briefly introduce recent novel approaches that MSCs enhanced therapeutic potentials of other cells for cardiac repair.
Mesenchymal Stem Cells as a Potential Therapy for Cardiovascular Diseases: A Mini-review
2015
The abnormal structural and functional change in arteries, heart, veins and capillaries directly leads to different cardiovascular disorders (CVD), including atherosclerosis. The main objective of this review is to evaluate the use of stem cell research in the treatment of cardiovascular diseases. Annually more people die from CVDs than from any other cause. This disease remains the major cause of death in United States, while in low and middle income countries it is responsible for about 80% deaths. Annually almost 20% deaths worldwide take place due to CVD. The factors which contribute to this disease include age, systolic and diastolic blood pressure, environmental factors, smoking status etc. Most cardiovascular diseases can be prohibited by counseling about behavioral risk factors such as tobacco use, unhealthy diet, obesity, physical inactivity and harmful use of alcohol. Individuals who are suffering from this disease or those at high risk need early detection and management ...
Emerging role for bone marrow derived mesenchymal stem cells in myocardial regenerative therapy
Basic research in cardiology, 2005
Current treatments for ischemic cardiomyopathy are aimed toward minimizing the deleterious consequences of diseased myocardium. The possibility of treating heart failure by generating new myocardium and vascular tissue has been an impetus toward recent stem cell research. Mesenchymal stem cells (MSC), also referred to as marrow stromal cells, differentiate into a wide variety of lineages, including myocardial and endothelial cells. The multi-lineage potential of MSCs, their ability to elude detection by the host immune system, and their relative ease of expansion in culture make MSCs a very promising source of stem cells for transplantation. In addition, emerging experimental results with MSCs offer novel mechanistic insights into cardiac regenerative therapy in general. Here we review the characterization of MSCs, animal and human trials studying MSCs in cardiomyogenesis and vasculogenesis in postinfarct myocardium, routes of delivery, and potential mechanisms of stem cell repair.
Mesenchymal stem cell therapy for heart disease
Vascular Pharmacology, 2012
Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in the bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, because of their easy preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vascular cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and may greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. In this review we will focus on the current understanding of MSC biology and MSC mechanism of action in cardiac repair.