Recent Developments in Cardiovascular Stem Cells

Abstract

45Human embryonic stem cells have been shown to differentiate to beating cardiomyocytes, SA nodal-like cells and mesodermal Recent Developments in Cardiovascular Research:The goal of "Recent Developments" is to provide a concise but comprehensive overview of new advances in cardiovascular research, which we hope will keep our readers abreast of recent scientific discoveries and facilitate discussion, interpretation, and integration of the findings. This will enable readers who are not experts in a particular field to grasp the significance and effect of work performed in other fields. It is our hope and expectation that these "Recent Development" articles will help readers to gain a broader awareness and a deeper understanding of the status of research across the vast landscape of cardiovascular research-The Editors. 50 Moreover, the use of induced pluripotent stem cell-derived cardiac myocytes for cardiac repair is hampered by their immature phenotype and the presence of epigenetic and genetic changes.24,51,52 Resident and bone marrow cells and cortical bone-derived cells are considered as potential sources for differentiation to cardiac myocytes but lacking compelling evidence for cardiac myogenesis and perhaps exerting their salutary biological effects through paracrine mechanisms. 19,29,[53][54][55][56][57][58] Equally exciting and challenging are the discovery and characterization of other CPCs that could give raise to various cardiac cells types, including smooth muscle cells, endothelial cells, and fibroblasts. [59][60][61][62][63] An important problem to overcome is the multiple comorbidities and their comedications of ischemic heart disease patients with heart failure that may affect cytoprotective signaling triggered by the different stem cell, as well as survival and differentiation properties of such stem cells in the injured tissue. [64][65][66] Clearly, the rapid face of discoveries is dazzling and a complete coverage of the recent developments in cardiovascular stem cells would be beyond the scope of this article. We regret that many valuable works were not covered in part or at all included in the present overview on Recent Developments. Clinical Trials In Human PatientsThe ClinicalTrials.gov lists >1000 clinical trials including >600 studies in the United States alone that tests effects of various stem cells in human patients (http://www.clinicaltrials. gov/). The list includes 71 including 38 active clinical trials in patients with heart failure using various stem cells, such as adipose-derived, mesenchymal, human embryonic, autologous CD133 + and CD34 + stem cells among the others.18,67-74Autologous skeletal myoblasts were probably the first cell type used to regenerate functional myocardium. It was tested initially in a rabbit model of myocardial cryoinjury, which showed incorporation of the injected myoblasts and improved myocardial performance. 75 Subsequent observational studies were followed by randomized clinical trials in human patients with heart failure injected with autologous skele...

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

“…MSC‐conditioned medium increases capillary density and preserves cardiac function 31. Recent clinical trials have suggested that secretion of paracrine factors may be the underlying mechanism responsible for the improvement in outcomes 4. In this study, we found that epicardial transplantation of MSC‐loaded patch enhances sustained production of Tβ4, HIF‐1α and VEGF by the engrafted cells and infarcted cardiac tissue and is more effective for simulating the epicardium compared with intramyocardial MSC transplantation.…”

“…Resent preclinical studies and clinical trails have shown that stems cell transplantation may be an effective way to improve cardiac function and attenuate adverse ventricular remodelling of the ischaemic myocardium 3, 4. There are several candidate stem cells for cardiac transplantation that have been recently evaluated 5, 6.…”

Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

“…Nevertheless, the mechanisms underlying the beneficial effects of MSCs are not completely understood. In addition, several important questions regarding the delivery method and route, the amount of injected cells, and the timing for stem cell transplantation are among the factors that may limit cell-based therapies in the treatment of ischemic heart disease [9,10,53]. These issues, undoubtedly, require further studies to optimize the cell therapy approaches, and represent a focus of future research in this field [9,10,53].…”

“…MSCs therapy is an ongoing approach to repair the heart in preclinical and clinical studies after cardiac events and has brought positive results [8][9][10]. Despite the evidences that MSCs reduce left ventricular dilatation [11], increase vascular density [12,13], decrease the extent of the infarcted area [9,11], reduce the apoptosis, and necrosis of cardiomyocytes [11,14], more consistent results from stem cell therapy in heart diseases may, indeed, be achieved through rigorous clinical trials, amount of cells providing maximal efficiency, optimal time frame for transplant, best procedures to manipulate the cells, and via of administration [8,9].…”

Evolving targeted therapies for right ventricular failure

“…The importance of promoting CPC lineage specification demonstrated in the C-CURE study has fueled exploration of other avenues of in vitro and in vivo lineage specification by biomaterials, cytokines, growth and trophic factors, miRNAs, co-culture and formulation of combinatorial approaches of cell clusters and chimeras [114]. Biomaterials including cardiac-specific cellularized or decelluarized matrices coated with stem cells, growth, trophic and mitotic factors, chemotactic factors or cytokines to facilitate CPC survival, vascularization, migration and serve as reservoirs for delivery of these growth and/ or trophic factors may extend the benefits of cell therapy and afford novel opportunities for tissue re-engineering [124]. There is growing enthusiasm for use of allogeneic stem cells, particularly hypoimmunogenic stem cells such as hMSCs or engineered cells, given ease of procurement, advanced preparation and the generally reduced secretory and proliferative potential of autologous stem cells prepared from patients with acute and chronic heart failure [88,106].…”