The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy

Hindawi Publishing Corporation Stem Cells International Volume 2015, Article ID 135023, 13 pages http://dx.doi.org/10.1155/2015/135023 Review Article The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy Xianyun Wang,1 Jun Zhang,1 Fan Zhang,1 Jing Li,1,2 Yaqi Li,3 Zirui Tan,4 Jie Hu,5 Yixin Qi,6 Quanhai Li,1,2 and Baoyong Yan1 1 Cell Therapy Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei 050017, China 3 Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China 4 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China 5 School of Nursing, Hebei Medical University, Shijiazhuang, Hebei 050000, China 6 Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China 2 Correspondence should be addressed to Quanhai Li; and Baoyong Yan; yanby Received 23 March 2015; Accepted 6 May 2015 Academic Editor: Joost Sluijter Copyright © 2015 Xianyun Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34+ and CD 133+ stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient’s physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future. 1. Introduction Reduced blood supply in infracted myocardium is the leading cause of morbidity and mortality in patients with ischemic cardiomyopathy (ICM) [1, 2]. While approximately 1% of adult cardiomyocytes possess ability of self-renewal, they cannot afford heart tissue impairment from serious or acute myocardial infarction [3–5]. Thus, ischemia-induced cardiomyocyte apoptosis and necrosis damage left ventricle geometry undergoing progressive ventricle remodeling, hypertrophy, and fibroblast proliferation resulting in scar information and poor contractility of left ventricle [6–8]. The common treatment strategies such as pharmacotherapy, coronary artery bypass grafting (CABG), and coronary artery stent enable the recovery of blood supply to the ischemic regions and relatively alleviate pain and suffering, but they fail to treat the pathophysiological changes following ischemic injury and regenerate novel muscle tissue. Therefore, the ideal treatment effect is to make myocardial cell regeneration resident cardiac progenitor cells or other exogenous multipotent stem cells [9]. Stem cell implantation treatment for ICM has brought a new dawn for patients while it faces a new challenge. Accumulating evidences have reported that stem cells repaired damaged heart by the means of differentiation to cardiac muscle cell, promoting angiogenesis, forcing proliferation of endogenous cardiac stem cells, and secreting cytokines, chemokines, and growth factors to activate endogenous reparative responses, inhibit cell apoptosis and fibrosis, and improve myocardial contraction [10]. In the last 2 decade, many clinical trials have been implemented to assess the safety, feasibility, and efficacy of stem cell administration in patients with ischemic cardiomyopathy. Different cell types including bone marrow-derived stem cells, mesenchymal stem cells (MSCs), cardiac-derived stem cells (CSCs), skeletal myoblasts (SMs), and hematopoietic stem cells (HSCs) have been used to evaluate the cell-based therapeutic potential. However, promising results from most clinical studies to improve functional parameters have yielded to the few mixed ineffective treatments. Delivery modalities, cell types and dose, cell isolation procedures, and timing of cell transplantation may determine the curative effect on cardiac functional recovery [11–13]. Here, the current status of clinical research and future outlook of stem cell-based therapeutics for ischemic cardiomyopathy are elaborated. 2. Types of Stem Cell and Their Clinical Studies In the last two decades, many different stem cell populations have been investigated and suggested to enhance cardiac function recovery in clinical trials. These stem cells can be categorized according to their cellular structure, function, origin, or cell surface marker, transcription factor, and specific protein. The simplest and most common way to group them depends on their site of origin. Stem cells isolated from heart are named cardiac-derived stem/progenitor cells and other types of stem cells are known as extracardiac-derived stem cells. Here, recent clinical trials of stem cell replacement therapy for ICM are described in Table 1. 2.1. Cardiac-Derived Progenitor/Stem Cells. In 2003, cardiac stem cells (CSCs) were first discovered by Nadal-Ginard and colleagues [14] which break the traditional idea that heart was terminal differentiated organ. The multipotent and self-renewing characteristics of these cells have been identified in animal models which showed their ability to give rise to cardiomyocytes, endothelial cells, and smooth muscle cells indicating a potential regenerative capacity of adult heart [15]. The experimental studies have reported that cardiomyocyte lineages can be derived from different types of cardiac stem cells including c-kit+ cell, isl-1+ cell and sca-1+ cell (restricted to murine hearts), and cardiosphere-derived cells (CDCs) [16]. CDCs are isolated from cardiac biopsies and grow as self-adherent clusters containing a heterogenous cell population of stem cells positive for c-kit (endogenous CSCs), CD105, and CD90 (cardiac MSCs) but negative for CD 45 (hematopoietic stem cell) indicating their capacities of clonogenic, self-renewal, and multilineage differentiation [17]. Accumu (...truncated)