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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Stem cells in cardiac repair in an inflammatory microenvironment
P Rameshwar1, H Qiu, S F Vatner
1Department of Medicine, New Jersey Medical School-UMDNJ, Newark, NJ, USA. rameshwa@umdnj.edu
Insights
Stem cell therapy shows promise for heart repair, but challenges remain in translating research to patients. Understanding microenvironmental factors like cytokines is crucial for effective cardiac tissue regeneration.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Cardiovascular disease is the leading cause of death in the US, with myocardial ischemic disease causing significant heart failure.
- Cardiac transplants are limited by supply, cost, and immunosuppression issues.
- Stem cell therapy offers a potential alternative for replacing damaged heart muscle cells.
Purpose of the Study:
- To review current literature on stem cell therapy for myocardial infarction and heart failure.
- To identify key areas for future research in cardiac stem cell applications.
- To highlight the role of microenvironmental factors, particularly cytokines, in stem cell responses.
Main Methods:
- Review of existing scientific literature and experimental studies.
- Focus on mesenchymal stem cells (MSCs) and their immune properties.
- Analysis of the influence of cytokines and other parameters on stem cell therapy outcomes.
Main Results:
- Stem cell therapy for cardiac repair has not yet been effectively translated to clinical practice.
- Mesenchymal stem cells (MSCs) exhibit immune plasticity (both immune-enhancing and -suppressing functions).
- Cytokine delivery and stem cell mobilization strategies yield varied results based on injury, patient factors, and other parameters.
Conclusions:
- The immune plasticity of MSCs is critical for successful tissue repair and gene delivery in cardiac applications.
- Further research is needed to optimize stem cell therapy by considering microenvironmental factors and patient-specific parameters.
- Exploring various stem cell sources, including placenta, cord blood, and cardiac stem cells, is important for future therapeutic development.
Abstract:
Despite advances in clinical interventions, drug therapy and preventative strategies for cardiovascular disease, heart disease remains the number one cause of death in the United States. A major cause of heart failure leading to death is myocardial ischemic disease. Terminal heart failure can be salvaged in some cases by cardiac transplants, but this therapeutic approach is limited by lack of supply, high cost, and problems with immunosuppression. An attractive alternative approach proposed over the last 1-2 decades is the replacement of myocardium at the level of the myocyte, which has focused on stem cell therapy. This form of therapy has been successful for hematopoietic replacement. Similar therapy has been proposed to treat hearts ravaged by ischemic necrosis and apoptosis. However, the experimental studies have not been effectively translated to patients with myocardial infarction or heart failure. This review discusses the current literature and points out key studies that are required for future directions, focusing on key roles for microenvironmental factors, such as cytokines, in stem cells responses when placed at sites of cardiac injuries. In the case of mesenchymal stem cells (MSCs), they exert both immune- enhancer and -suppressor functions, which are referred to as immune plasticity. This type of immune properties by MSCs is significant to therapeutic outcomes. Thus, the plasticity of MSCs, with regards to immune responses, has to be considered carefully in tissue repair and replacement and in gene delivery systems. The route by which cytokines are delivered as adjuvant to cell therapy, or as methods to mobilize stem cells, will show varied results, depending on the degree of injury, underlying clinical disorders and other diverse parameters, such as ethnicity, age and genomic profile. In addition to MSCs, roles exist for other stem cells, such as those from placenta, cord blood, hematopoietic stem/progenitor cells and cardiac stem cells.

