Stem Cell Treatments for Coronary Artery Disease
For the past 70 years, the leading cause of death throughout the world has been heart disease--more specifically, Coronary Artery Disease (CAD) (1). Caused by the buildup of a wax-based plaque within the coronary arteries, CAD has been shown to significantly decrease life expectancy. However, the survival rate also depends on factors that include age, overall health, patient history, and condition severity (2).
Coronary Artery Disease is caused when the arteries that supply blood to the heart become narrowed or blocked due to fat deposits. This buildup of fat creates plaque that hardens the arteries, which prevents the efficient movement of blood to the heart muscle that sustains it and allows it to pump blood to the rest of the body. As a result, myocardial cells begin to die (4). Since the heart cannot regenerate them, these cells may be replaced with scar tissue that oftentimes cannot support contractions, leading to chest pain, shortness of breath, or, in severe cases, heart attacks. When this persists, the long-term effects may include heart failure, arrhythmias, and increased risk of a sudden cardiac arrest from the weakened heart muscle. CAD also triggers an inflammatory response that contributes to heart failure in the infarct area (5).
Given how dependent effective heart surgery is on technological advancements, many of the treatments for CAD are relatively new. Scientists have spent many years working to improve treatments for heart diseases, and so far, they have only seen advancements in minimally invasive surgical techniques (6). However, recent advancements in regenerative medicine and stem cell therapies have provided an innovative approach that leverages Mesenchymal stem cells (MSCs) to repair and even replace damaged heart tissues (7).
The role of stem cells in CAD treatment is to restore cardiac function by regenerating the heart muscle cells (7). Specifically, MSCs are undifferentiated stem cells taken from the patient's bone marrow or adipose tissue and grown in a culture where they can proliferate and differentiate into cardiomyocytes (8). They are then injected into the damaged areas of the heart or administered intravenously to restore the heart's function and promote healing. Researchers have similarly explored the potential of these stem cells to help grow complete tissues that can be used for transplantation and repair damaged heart tissue (7).
Over the years, the typical treatments for CAD included open heart surgery, Coronary Artery Bypass Grafting (CABG), percutaneous coronary interventions (PCI) such as angioplasty and stenting, and in some extreme cases, heart transplantation. These treatments, however, can only prevent further progression, not restore cell function. Additionally, they bear several operational limits, and often, there are not enough donor organs available to carry out transplants (8). MSCs, on the other hand, can differentiate into new heart cells, which regenerate muscle and tissue and also secrete growth factors and anti-inflammatory molecules for the healing process.
Recent studies have shown promising results that support the use of MSC therapy. A meta-analysis involving 11 controlled trials indicated that MSC treatment led to an increase in Left Ventricular Ejection Fraction (LVEF), the amount of blood that is pumped out of the left ventricle with each contraction, demonstrating improved heart function for the recipients of MSCs (7)(8). White blood cell suppression and anti-inflammatory responses were also detected, which helped manage the inflammatory response. MSCs have also been shown to reduce the formation of scar tissue and even increase the patient's exercise capabilities (8).
While these results seem promising, several limitations must be overcome before MSCs can be fully integrated into CAD treatment. Primarily, there is a lot of variance in the effectiveness of stem cells from one person to another. Researchers have noticed that patients tend to respond differently to the treatment based on the culturing, timing, dosage, and delivery of the MSCs (12). For example, some studies have suggested that transendocardial injection of the MSCs may be more effective in treating CAD, while others have favored intravenous administration. In some cases, results are also influenced by how the cells were obtained and the overall health of the donor (8). Either way, identifying which patients are most likely to benefit from the therapy is an ongoing area of research, especially since external factors such as age or severity of CAD can also influence the treatment outcomes. Thus, given how personalized stem cell treatments can be, they are more challenging to implement universally.
Additionally, because stem cells are typically found in small amounts throughout the body and also have very limited division capabilities, it is challenging to obtain enough for clinical use (9). Some studies have even shown that MSCs tend to have a low survival rate and may disappear after a transplant, thus the long-term survival and function of these cells in the heart require further investigation (9). Another major obstacle is that the long-term effects of MSC are largely unknown since stem cell-based treatment is a new field. The potential risk of developing tumors from the stem cells after differentiation must be considered. Overall, more research is necessary to examine the survival and efficacy of stem cells before they are used further.
Continued research and advancements in technology have provided ways to overcome these limitations. New cell culture techniques such as spontaneous senescence, which maintain MSC populations for longer periods in culture, can limit cell death (11). Other scaffolding technology has been developed to improve the administration of MSCs, allowing them to attach and proliferate better. Additionally, several completed and ongoing trials of MSCs in heart disease indicated that MSC treatment is safe. There was no reported tumor development with the transplantation, though these trials are still in their earlier stages (11). They have similarly found that MSCs are generally well received and tolerated by the recipient because of their low immunogenicity, significantly reducing the chance of outright rejection by the patient (10). In the coming years, new delivery methods, such as engineered biomaterials or nanoparticles, which are currently being researched, could help improve the survival of transplanted cells (9). Ultimately, as more data becomes available, MSC treatment will likely become more standardized and cost-effective in a heart environment.
In conclusion, while coronary artery disease and heart disease in general have remained pressing global health issues, the emerging field of Stem Cell therapy has provided hope to millions of suffering patients. As this field expands and critical developments in research continue to be made, we are likely to witness significantly improved patient outcomes and more widespread use of MSC-based treatments. Hopefully, we will see cases of CAD decline worldwide.
References
American College of Cardiology. (2024, April). Journal of the American College of Cardiology. https://www.jacc.org/doi/10.1016/S0735-1097%2824%2904310-9
Texas Heart Institute. Coronary artery disease. https://www.texasheart.org/heart-health/heart-information-center/topics/coronary-artery-disease/
Centers for Disease Control and Prevention. (2024, May 15.). Heart disease data & statistics. https://www.cdc.gov/heart-disease/data-research/facts-stats/index.html
University of Michigan Health. Coronary artery disease (CAD). https://medicine.umich.edu/dept/cardiac-surgery/patient-information/adult-cardiac-surgery/adult-conditions-treatments/coronary-artery-disease-cad
National Center for Biotechnology Information. (2022, October 26). Inflammation and atherosclerotic plaques are recruited to initiate plaque development. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9742007/
Henry Ford Health. (2024, February 16). Advancements in heart care. https://www.henryford.com/blog/2024/02/advancements-in-heart-care
DVC Stem. (2024, June 11). Stem cells reverse heart disease. https://www.dvcstem.com/post/stem-cells-reverse-heart-disease
National Center for Biotechnology Information. (2023, Nov 28). Stem cell therapy for cardiovascular diseases: Current status and future directions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10706847/
ScienceDirect. (2023). Research progress on the application of mesenchymal stem cells in cardiovascular disease. https://www.sciencedirect.com/science/article/pii/S2666765723000662
National Center for Biotechnology Information. (2019, April 24). The low immunogenicity of the stem cells. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719501/
Nature. (2020). Recent advances in stem cell therapy for cardiovascular diseases. https://www.nature.com/articles/s41419-020-2542-9
Progencell. Stem cell therapy limitations. https://progencell.com/about-stem-cell-therapy/stem-cell-therapy-limitations/
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