Stem cells for cardiac repair in acute myocardial infarction (original) (raw)
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Journal of Stem Cell Research, 2021
Myocardial infarction (MI) results in irreversible loss of cardiomyocytes (CMs) and can often lead to heart failure. Due to the minimal regeneration capacity of the myocardium, novel therapeutic techniques are needed. Cell therapy has emerged as a promising treatment for MI and involves the introduction of stem cells into the infarct area where they can proliferate and regenerate functional heart tissue. These cells can be delivered by various methods, including direct injection, scaffold formation, and cell sheet preparation. Of these, cell sheet technology appears to hold the most promise as it allows for maximal cell engraftment and retention without significant harmful side effects. Furthermore, the best composition of the cell sheet has since been debated. Cell sheets composed of skeletal myoblasts (SMs), mesenchymal cells (MSCs), and pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have proven to be of the greatest interest for engraftment into infarcted myocardium. Due to their vast differentiation and proliferation potential, pluripotent stem cells show a unique ability to readily regenerate functional myocardium following transplantation. iPSCs express the same pluripotency and induce similar effects in vivo as human ESCs, while circumventing certain sourcing problems and controversies, making them a favorable alternative Identification of an effective combination cell delivery method that allows for prolonged improvement in heart function while decreasing rates of cell death would represent a major advancement in stem cell therapy and the clinical treatment of MI.
Stem cells for myocardial repair
Thrombosis & Haemostasis, 2010
There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myocardial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy.
USE OF STEM CELL THERAPIES FOR REGENERATION OF DAMAGED HEART TISSUE AFTER ACUTE MYOCARDIAL INFARCTION (Atena Editora), 2023
Objective: To analyze the current literature on the use of stem cell therapies for the regeneration of injured cardiac tissue after acute myocardial infarction. Methodology: Bibliographic review study through searches in PubMed databases, published from 2017 to 2022, totaling 11 studies used to compose the bibliographic review. Results: The studies demonstrate that different types of stem cells can be used, including embryonic stem cells, induced pluripotent stem cells and skeletal myoblasts. Several mechanisms of action of stem cells occur, including the release of exosomes, the modulation of the inflammatory response, the regulation of gene expression and the interaction with the extracellular matrix. Clinical evidence has shown that stem cell transplantation can result in significant improvements in cardiac function, including increased left ventricular ejection fraction and reduced ventricular volume of muscle and intraventricular cavity. These encouraging results underscore the therapeutic potential of stem cells in regenerating heart tissue and treating cardiovascular disease. Conclusion: It is important to highlight that further studies are needed to deepen the understanding of the mechanisms of action of stem cells and their clinical application, seeking to improve the efficacy and safety of stem cell therapies for heart disease and other medical conditions.
Myocardial Regeneration and Stem Cell Repair
Current Problems in Cardiology, 2008
Recent evidence would suggest that the heart is not a terminally differentiated organ and has the ability to regenerate itself under normal and pathophysiologic conditions. A major effort has been made to identify precursor cells that are capable of differentiating into cell lineages different from their organ of origin. Embryonic stem cells and bone marrow-derived cells (BMCs) have been studied and characterized, and BM precursor cells are currently being utilized as therapy in clinical trials of patients with heart failure of ischemic and nonischemic etiologies. Controversy remains, however, whether BMCs are the best cells to be used for replacement therapy. The existence of a cardiac stem cell (CSC) has also been described, which has the ability to generate new cardiac myocytes and blood vessels, raising the possibility of rebuilding a damaged heart with the organ's own precursor stem cell population. Animal studies have suggested such a possibility, and a clinical trial using CSCs is in progress. This monograph discusses our current understanding of myocardial regeneration and the roles that endogenous and exogenous stem cells may have in the future therapy of cardiovascular disease. (Curr Probl Cardiol 2008;33:91-153.) C ardiovascular diseases, including acute myocardial infarction and congestive heart failure, are the leading causes of death in the industrialized world. The epidemic problem of heart failure, Funded research work from the National Institutes of Health. The authors have no conflicts of interest to disclose. Curr Probl Cardiol 2008;33:91-153.
Clinical applications of stem cell therapy for regenerating the heart
Acta medica Indonesiana, 2010
An immediate reperfusion therapy after acute myocardial infarction (AMI) is a prerequisite to prevent further cardiac damage and minimize ventricular remodelling. Although a rigorous and sophisticated set of therapeutic procedure has been applied in the disease management, mortality rate has yet unchanged during the last twenty years. This fact necessitates an alternative or adjuvant therapy that is critically safe and capable of repairing the injured vascular as well as regenerating the infarcted myocardium without omitting the ethical considerations. Stem cell therapy could be the answer. It has gained major basic and clinical research interest, ever since its discovered potential to repair the injured vascular in 1997. Multiple cell types across lineages have been shown to be able to transdifferentiate into mature functioning cardiomyocytes either in vitro through similar phenotypical and genotypical characteristics or in vivo by regenerating the infarcted myocardium and improve ...
From bench to bedside, work in cell-based myocardial regeneration therapy
In clinical cellular cardiomyoplasty, bone marrow cells and myoblasts are introduced mainly to ischemic cardiomyopathy tissue via several cell delivery systems, such as needle injection or catheter. These clinical studies have demonstrated the safety and feasibility of this technique, but its effectiveness for treating heart failure, especially in the long term, is still under discussion. Neither of these cell types can differentiate into cardiomyocytes; rather, they improve the failing heart mainly by the paracrine effects of some cytokines, such as Hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF). Thus, many researchers have a great interest in stem cells, which exist in bone marrow, circulating blood, atrium, and adipose tissue, and can differentiate into cardiomyocytes. Although several stem cells with the potential to differentiate into various cell types have been reported, few can differentiate into cardiomyocytes. Moreover, beating cells that can demonstrate synchronized contraction with native cardiomyocytes are critical for the complete repair of severe heart failure. Therefore, stem cells with a high differentiation capacity should be explored for the goal of completely repairing severely damaged myocardium. In this review, we summarize the clinical protocols and basic experiments for cellular cardiomyoplasty using bone marrow cells, myoblasts, and other stem cells.
Stem cell-based therapies for heart regeneration: what did the bench teach us?
Cardiovascular & hematological disorders drug targets, 2010
Stem cell-based therapies represent a promising therapy for myocardial infarction. Pre-clinical and clinical tests performed in the last 10 years indicate that several types of stem cells and their progenies reduce infarct size and improve cardiac contractile function. The mechanism is dependent on the type of cell and involves a combination of several factors, such as: (i) the formation of new blood vessels, (ii) the release of pro-survival, pro-angiogenic and anti-inflammatory factors (paracrine effect), and (iii) the functional contribution of cardiomyocytes. With the exception of cardiac progenitor cells and pluripotent stem cells (human embryonic stem cells and inducible pluripotent stem cells) that have the unquestioned ability to give rise to cardiomyocytes, the other stem cells, including bone-marrow stem cells and fetal stem cells, have none or very limited capacity to differentiate into contractile cells. For both cases, it is of the utmost importance to develop strategies...
13 Stem Cell Therapy for Myocardial Regeneration
Myocardial regeneration through stem cell therapy is a relatively new concept that has the potential to help millions of patients with ischemic heart disease and congestive heart failure. Proof of concept for stem cell-mediated angiogenesis and myocardial regeneration was established in early animal studies; data from subsequent phase I and II human clinical trials are encouraging. Autologous skeletal myoblasts are the most extensively studied stem cells and appear to be relatively safe and efficacious when injected directly into the myocardium, either through an open-chest or percutaneously. The occurrence of arrhythmogenicity remains an issue, however. Other bone marrow stem cell preparations have also shown promise in improving left ventricular function at follow-up, however these improvements may not be sustained. Refinements in the types of cells delivered and the mode of delivery may lead to more substantial and long-lasting results. The use of granulocyte colony-stimulating factor to augment the body's natural mobilization of bone marrow-derived stem cells to damaged myocardium has not been proven to be useful based on clinical studies available to date. Future challenges include determining the appropriate type, dose, timing, and delivery of cells, as well as identifying the subset of patients who are most likely to derive benefit.