Stemcell Research & Evidence - Heart Conditions
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Cardiac Regeneration and Stem Cells
Physiol Rev. 2015 Oct;95(4):1189-204.
Center for Cardiovascular Biology, Institute for Stem Cell Research and Division of Cardiology, Departments of Medicine and Pathology, University of Washington, Seattle, Washington.
After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.
Heart regeneration using pluripotent stem cells
J Cardiol. 2020 Nov;76(5):459-463.
Department of Regenerative Science and Medicine, Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Pluripotent stem cells (PSCs), which include embryonic and induced pluripotent stem cells (ESCs and iPSCs, respectively), have great potential in regenerative medicine for heart diseases due to their virtually unlimited cardiogenic capacity. Many preclinical studies have described the functional benefits after transplantation of PSC-derived cardiomyocytes (PSC-CMs). However, transient ventricular arrhythmias were detected after injection into non-human primates and swine ischemic hearts; as engrafted PSC-CMs form an electrical coupling between host and graft, the immature characteristics of PSC-CMs may serve as an ectopic pacemaker. We are entering a critical time in the development of novel therapies using PSC-CMs, with the recent first clinical trial using human iPSC-CMs (hiPSC-CMs) being launched in Japan. In this review, we summarize the updated knowledge, perspectives, and limitations of PSC-CMs for heart regeneration.
Combined usage of stem cells in end-stage heart failure therapies
J Cell Biochem. 2014 Jul;115(7):1217-24.
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.
Remarkable achievements have been made in the clinical application of mechanical circulatory support and cardiac transplantation for patients with end-stage heart failure. Despite the successes, complications associated with these therapies continue to drive cardiac regenerative research utilizing stem cell based therapies. Multiple stem cell lineages hold clinical promise for cardiac regeneration-mostly through cellular differentiation, cellular fusion, and paracrine signaling mechanisms. Bone marrow-derived endothelial progenitor cells are among the most intriguing and controversial cell types currently being investigated. Formidable barriers exist, however, in finding the ideal cardiac regenerative stem cell, such as identifying specific lineage markers, optimizing in vitro cellular expansion and improving methods of stem cell delivery. Hybrid approaches of cardiac regeneration using stem cell therapies in conjunction with immunomodulation after cardiac transplantation or with mechanical circulatory support produce cutting edge stem cell technologies. This review summarizes the current knowledge and therapeutic applications of stem cells in patients with end-stage heart failure, including stem cell therapy after implantation of mechanical circulatory support and cardiac transplantation.
Regeneration of the heart
EMBO Mol Med. 2011 Dec;3(12):701-12.
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Partners Research Building, Cambridge, MA, USA.
The death of cardiac myocytes diminishes the heart's pump function and is a major cause of heart failure, one of the dominant causes of death worldwide. Other than transplantation, there are no therapies that directly address the loss of cardiac myocytes, which explains the current excitement in cardiac regeneration. The field is evolving in two important directions. First, although endogenous mammalian cardiac regeneration clearly seems to decline rapidly after birth, it may still persist in adulthood. The careful elucidation of the cellular and molecular mechanisms of endogenous heart regeneration may therefore provide an opportunity for developing therapeutic interventions that amplify this process. Second, recent breakthroughs have enabled reprogramming of cells that were apparently terminally differentiated, either by dedifferentiation into pluripotent stem cells or by transdifferentiation into cardiac myocytes. These achievements challenge our conceptions of what is possible in terms of heart regeneration. In this review, we discuss the current status of research on cardiac regeneration, with a focus on the challenges that hold back therapeutic development.
Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases
J Cell Biochem. 2018 Jan;119(1):95-104.