Short assessment on cell-based therapies
Received: 05-Apr-2022, Manuscript No. puljhr-22-4757; Editor assigned: 08-Apr-2022, Pre QC No. puljhr-22-4757 (PQ); Accepted Date: Apr 08, 2022; Reviewed: 16-Apr-2022 QC No. puljhr-22-4757 (Q); Revised: 21-Apr-2022, Manuscript No. puljhr-22-4757 (R); Published: 30-Apr-2022, DOI: 10.37532/puljhr.22.5(2).16-18
Citation: Stewart H. Short assessment on cell-based therapies. J Heart Res. 2022; 5(2): 16-18.
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Abstract
Globally, Congestive Heart Failure (CHF) caused by chronic coronary artery disease is a leading cause of morbidity and mortality. Despite breakthroughs in medical and device therapy, its prevalence is rising. Adult stem cell therapies have emerged as a viable treatment for creating new cardio-myocytes and arteries, and they are expected to reverse functional decline in patients with congestive heart failure who are not candidates for heart transplantation. The greatest favorable outcomes from cell therapy are related with paracrine actions rather than direct differentiation, according to research conducted over the last two decades. Paracrine substances produced by stem cells, such as growth factors, cytokines, and microRNAs reduce scar volume and myocyte apoptosis, boost myocyte proliferation, and activate endogenous cardiac stem cells to create new myocytes.
Keywords
Congestive heart failure; Myocardial Infarction (MI); Adult stem cells; Mesenchymal stem cells; Cardiac stem cells
Introduction
Congestive Heart Failure (CHF) caused by chronic coronary artery disease is a leading cause of morbidity and mortality. Despite breakthroughs in medical and device therapy, its prevalence is rising. Neurohormonal activation (e.g., the renin-angiotensin-aldosterone system, the sympathetic nervous system, and arginine vasopressin) is reduced, reducing myocyte apoptotic cell death and interstitial connective tissue proliferation, and slowing the progression of myocyte cellular hypertrophy with currently available medical interventions [1]. However, none of the current treatments are successful in correcting myocyte loss and cellular abnormalities linked to poor myocyte contractile performance in the failing heart. As a result, cardiac transplantation has been the only treatment option for those with severe heart failure [2]. Cell-based therapy has emerged as a promising new treatment option for restoring damaged heart function. Cell-based research has received a lot of attention over the last two decades. Experiments have shown that producing new cardio-myocytes and arteries, reversing functional degradation, and slowing the course of CHF can all be beneficial [3]. In addition, in vivo experiments demonstrated that the most favourable benefits of cell treatment are linked to paracrine actions rather than direct tissue regeneration. Paracrine substances (such as growth factors, cytokines, and microRNAs) are secreted by stem cells, which reduce scar volume and myocyte apoptosis, boost myocyte proliferation, and activate endogenous cardiac stem cells to create new myocytes. Preclinical findings from animal models led to multiple clinical trials evaluating the safety of autologous and allogeneic stem cells and progenitor cells in humans. Their clinical significance, however, is still unknown. As a result, the majority of clinical studies' therapeutic results are minimal at best. The disparities between animal research and several clinical trials necessitate a re-evaluation of current cell-therapy procedures.
We will describe existing therapy limits and alternative options that have been evaluated in the experimental and clinical sectors in the following sections.
Low cell retention associated with cell delivery approach
Intravenous, intramyocardial (epicardial or subendocardial), and intracoronary injections are the three major cell delivery techniques that have been tested in clinical applications so far. Cells were administered systemically for intravenous injection, however just 0.04% of cells reached the heart, with the bulk imprisoned in other organs (i.e., lung, kidney, liver and spleen). Intramyocardial and intracoronary injection techniques provide higher cell retention results [4]. However, within minutes of intramyocardial or intracoronary stem cell injection, the vast majority of cells (85%) are washed out through the coronary venous system or mechanically ejected from the injection site, with only 1%-2% remaining in the heart one month later. As a result, numerous techniques are being examined to improve cell survivability, improve functional qualities of individual stem cells, and prolong cell retention in order to maximize their regenerative effects on the myocardium.
Enhancement of cell viability and functional properties with genetic modification
Mesenchymal Stem Cells (MSCs) generated from bone marrow have been used to analyze genetic alteration the most. Allogeneic MSCs are immunoprivileged because they lack the expression of The Major Histocompatibility Complex (MHC) class II antigen, which allows them to avoid direct detection by helper T-cells [5]. Clinical research has established the safety and usefulness of MSCs, and there is growing interest in boosting the benefits of MSC therapy. Combining MSCs with pharmacotherapy, genetically altering MSCs, and preconditioning MSCs, for example, are all being investigated as ways to improve MSC-mediated heart repair [6].
MSCs that have been transfected with the Akt or cell survival protein improve myocardial protection. In addition, MSCs modified to express a mix of gene products including Akt and angiopoietin-1 (Ang1) has showed functional improvements in animal models. By activating the Akt pathway, MSCs overexpressing Vascular Endothelial Growth Factor (VEGF) and Stromal Cell-Derived Factor-1 (SDF-1) improve heart function. In a cardiac ischemia reperfusion paradigm, MSCs transfected to express Heme-Oxygenase-1 (HO-1), an enzyme that improves MSC tolerance to hypoxia, improve EF and lower end systolic volume compared to controls [7]. Although these preconditioned MSCs improve engraftment and survival of transplanted cells, clinical application is unjustified due to safety concerns about genetic change of the stem cell nucleus.
Combination of mesenchymal stem cells and cardiac stem cells
Another strategy is to combine Mesenchymal Stem Cells (MSC) and Cardiac Stem Cells (CSC) to boost each cell type's therapeutic effects. While all stem cell-treated animals improved their left ventricular ejection fraction when compared to placebo controls, animals receiving dual cell therapy had a 2-fold greater reduction in scar size (21.1% for CSC/MSC versus 10.4% for CSC alone or 9.9% for MSC alone) and improved diastolic pressure change rates. Both the combination treatment and CSC or MSC alone treated groups improved overall left ventricular chamber dynamics [8]. Intriguingly, CSC alone treated animals had better isovolumic relaxation than controls, while MSC alone treated animals had better diastolic compliance, suggesting that the enhanced effect of dual therapy on both systolic and diastolic function could be due to a synergistic effect between CSC and MSC targeted mechanisms. A clinical investigation is currently underway to evaluate the therapeutic effects.
Repeated Stem Cell Injection
Due to the lack of expression of MHC class II antigen, allogeneic MSCs and CDCs are immunoprivileged and can avoid direct identification by helper T-cells. Based on these findings, a clinical trial including allogeneic human MSC/CDC therapy in patients with persistent myocardial infarction was recently launched (POSEIDON51, ALLSTAR59). Because a single injection of MSCs or CDCs has only a little effect on cardiac function and scar volume, it was assumed that repeated stem cell injections would be more efficient in repairing myocardial tissue [9]. The initial infusion of cells, on the other hand, initiates and increases the immune response, while subsequent injected cells are swiftly removed and rendered ineffective. This rapid response is more commonly associated with acquired/adaptive immunity than with innate immunity. As a result, the development of effective MSC/CDC platforms that are provided with appropriate immune suppression could overcome the challenges of multiple stem cell injections and enable for the broad use of "off-the-shelf" cell therapy to treat the enormous number of patients in need. Immune-tolerant MSCs or CDCs could be created using gene-editing technologies to reduce acquired immunity [10].
Conclusion
Promising data gained from experimental models suggests that cell-based therapy could be successful in clinical settings. Early-stage clinical trials, on the other hand, are exposing therapeutic limitations. We need to rethink our current challenges and come up with new answers. Clinical outcomes are offering additional insight into the development of the second stage of cell-based therapeutic research. Adult stem cells (i.e., bone marrow mononuclear cells, adipose-derived stem cells, MSCs, CDCs, and CSCs) are ideal candidates for cell-based therapeutics due to their known safety profiles. The efficacy of stem cell therapy will be improved further by genetic alteration, preconditioning, biomaterials, bioengineering, cell combinations, and repeated injection techniques. The existing understanding of stem cell-based therapy, as well as upcoming approaches and discoveries, will undoubtedly advance cell-based therapy. Many CHF sufferers have received treatment and have been cured.
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