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Stem Cell Therapy for Heart Failure

Stem cells hold significant potential for the treatment of cardiovascular diseases, such as heart failure and coronary artery disease. A number of clinical trials have demonstrated the safety and effectiveness of stem cell therapy in improving heart function and reducing the risk of major adverse cardiovascular events.

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Stem Cell Therapy for Heart Failure

Louis A. Cona, MD
Updated on
Dec 13, 2023

Stem cells hold significant potential for the treatment of cardiovascular diseases, such as heart failure and coronary artery disease. A number of clinical trials have demonstrated the safety and effectiveness of stem cell therapy in improving heart function and reducing the risk of major adverse cardiovascular events.

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Stem cells hold significant potential for regenerating damaged cardiac tissue, offering a promising alternative to traditional treatments.

Stem cells are a type of cell that can develop into many different types of cells in the body. Stem cells can self-renew, meaning they can divide and produce more stem cells and differentiate, becoming specialized cell types such as heart muscle cells or blood cells.

The use of stem cells to regenerate damaged cardiac tissue holds significant potential because of their ability to differentiate into specialized cell types. In the case of cardiac disease, stem cells may be able to differentiate into new heart muscle cells and blood vessels, helping to repair and regenerate damaged tissue in heart failure.

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Stem cell heart repair treatment

Stem cell therapy offers a promising alternative to traditional treatments for cardiac disease and heart attacks, often involving medications, interventional procedures, or surgery to manage symptoms or improve blood flow to the heart.

While these treatments can be effective, they do not address the underlying problem of tissue damage and may not fully restore heart function. In contrast, stem cell therapy has the potential to directly address the underlying cause of Cardiac or Heart Disease by promoting tissue repair and regeneration.

Heart cell macro image

Stem cell treatment for low ejection fraction

Stem cell therapy has emerged as a promising treatment for patients with low ejection fraction, a condition characterized by heart attacks and by the inability of the heart to pump blood effectively. This therapy uses mesenchymal stem cells to regenerate damaged heart tissue and improve heart function by reducing inflammation and potentially regenerating scar tissue.

Mesenchymal stem cells have been shown in multiple studies to stimulate the growth of new blood vessels and heart muscle cells and improve the function of existing cardiac cells. This increases the heart's pumping ability, improving symptoms and overall quality of life for the patient.

Can stem cells treat heart disease?

Several clinical trials have demonstrated the safety and efficacy of stem cell therapy for low ejection fraction. In a meta-analysis of 23 randomized controlled trials, stem cell therapy significantly improved ejection fraction and reduced the risk of major adverse cardiac events compared to standard treatment or placebo. However, there are still some limitations to the widespread use of stem cell therapy for low ejection fraction. The optimal type of stem cells, dosing, delivery method, and timing of treatment are still under investigation, and the long-term effects of cardiac cell therapy are still unclear.

Congestive heart failure stem cell treatment

Congestive heart failure is when the heart cannot pump blood effectively, leading to fluid buildup in the lungs and other parts of the body. Stem cell therapy has been investigated as a potential treatment for congestive and heart failure patients.

Stem cells can differentiate into various types of cells, including heart cells. Studies have shown that stem cells can improve heart function in patients with congestive heart failure. Stem cells have been shown to stimulate the growth of new blood vessels and heart muscle cells, thereby improving cardiac function and blood flow and reducing inflammation in the heart.

model of human heart

Overview of Cardiac Disease and Current Treatments Options

Cardiac or Heart Disease is a range of conditions affecting the heart and its ability to function correctly. Some common examples of the cardiac disease include coronary artery disease (CAD), heart failure, and cardiomyopathy.

Various treatment options are available for cardiac disease, depending on the specific condition and its severity. Some common treatments include:

  1. Lifestyle changes: Changing diet and exercise habits can help improve heart health and reduce the risk of developing a cardiac disease.
  2. Medications: A range of medicines are used to treat cardiac disease, including aspirin and other antiplatelets to prevent blood clots, statins to lower cholesterol, and beta blockers to reduce blood pressure and manage arrhythmias.
  3. Interventional procedures: Procedures such as angioplasty and stenting can restore blood flow to the heart in cases of CAD.
  4. Surgery: In more severe cases of cardiac disease, surgery may be required to repair or replace damaged heart tissue. Examples include coronary artery bypass surgery and heart transplantation.
  5. Rehabilitation: After a cardiac event or procedure, rehabilitation programs can help patients recover and improve their heart health. These programs typically include exercise training and education on managing the cardiac disease.

What is acute myocardial infarction?

Myocardial infarction or heart attack occurs unless arteries in the heart have clots that form on top of plaques or a buildup of fat, cholesterol, calcium, or other substances. The body loses oxygen, the body's nutrients are destroyed, and large parts of the body are affected. In the case of a heart attack, scar tissue is usually replaced by damage to the heart muscle, and it also reduces the ability of the heart muscles to pump blood and heart rate effectively.

How are acute myocardial infarction and congestive heart failure currently treated?

Lifestyle changes, like reducing fat intake and calories, and exercising regularly, are recommended for heart health. These goals mitigate the risk of a new disease by limiting symptoms. Vascular surgeons usually use angioplasty to prevent and remove blood vessels and narrow clogged arteries. Angioplegia is the surgical procedure of inserting and inflating balloons inside the damaged arterial tissue.

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Benefits of MSCs in Coronary Artery Surgery

Patients who undergo coronary artery surgery can potentially benefit from the administration of MSCs, as these cells have been shown to aid in tissue repair and regeneration. By optimizing the delivery of MSCs, researchers hope to enhance their therapeutic effects and improve patient outcomes following coronary artery surgery.

What are stem cells?

Stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and tissues. There are two main types of stem cells: embryonic stem cells, which come from unused embryos resulting from an in vitro fertilization procedure, and adult stem cells, which come from fully developed tissues such as the umbilical cord, fat tissue (Adipose), and bone marrow. 

Stem cells can potentially develop into many different cell types in the body and can be used to replace damaged tissues. They are also used in clinical research trials to produce specialized cells like nerve or heart cells in the lab without taking tissue from patients.

What is the process of adult stem cell therapy for heart disease?

There are several steps involved in the process of adult stem cell therapy for heart disease:

  1. Procurement of stem cells: Adult stem cells can be obtained from various sources, including bone marrow, adipose tissue, and circulating blood. These cells are typically harvested through a minimally invasive procedure, such as a bone marrow aspiration or fat tissue biopsy. The cells can also be sourced from a donor, as is the case for umbilical cord tissue-derived stem cells.
  2. Preparation and expansion of stem cells: Once harvested, they are typically cultured in a laboratory setting to increase their numbers. This process, known as expansion, allows more stem cells to be used for treatment.
  3. Delivery of stem cells: There are several methods of delivering stem cells to the site of injury in the heart. These include intravenous injection, intracoronary injection, intracoronary infusion, and direct injection into the myocardium (the heart muscle tissue).
  4. Engraftment and differentiation of stem cells: After being delivered to the injury site or intravenously, the stem cells must engraft (attach and integrate) into the surrounding tissue. They then differentiate (develop into specialized cell types) and regenerate damaged tissue.
  5. Post-treatment monitoring: Patients will typically be monitored for any adverse effects and signs of heart function improvement after stem cell therapy. Follow-up imaging studies may be performed to assess the extent of tissue regeneration and reduction of inflammation.

Stem cell therapy for heart failure

Intravenous mesenchymal stem cell (MSC) treatment is safe and effective for cardiovascular diseases, including heart failure and coronary artery disease. In a systematic review of 11 clinical trials involving a total of 647 patients, doctors found that MSCs significantly improve left ventricular ejection fraction (LVEF), a measure of heart function, and reduce the incidence of major adverse cardiovascular events (MACE) worsening heart failure (Chung et al., 2017).

Another clinical trial involving 80 patients with ischemic heart disease found that MSC treatment was associated with a significant improvement in LVEF and a decrease in the size of infarcted (dead) heart tissue (Zhang et al., 2015).

Overall, the evidence suggests that intravenous MSC treatment is a promising therapy for most adults treating cardiovascular diseases, potentially improving heart function and reducing the risk of adverse events.

Types of stem cells used for cardiac regeneration

Mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) have shown great promise as a potential treatment for cardiovascular diseases. These stem cells, found in the connective tissue surrounding the umbilical cord, have been shown to have a high proliferative capacity and the ability to differentiate into various cell types, including human cardiomyocytes (heart muscle cells) (Zhang et al., 2017).

Several clinical trials have demonstrated the safety and effectiveness of WJ-MSCs for treating cardiovascular diseases. For example, a clinical trial involving 60 patients with ischemic heart disease found that treatment with WJ-MSCs was associated with a significant improvement in left ventricular ejection fraction (LVEF), a measure of heart function, and a reduction in the size of infarcted (dead) heart tissue (Wang et al., 2016).

In addition to their therapeutic potential, WJ-MSCs have several other advantages as a source of stem cells for cardiac regeneration. They can be easily obtained through a non-invasive procedure and have a low risk of an immune response or rejection, making them an attractive option for allogeneic (between individuals) transplantation (Zhang et al., 2017).

Overall, using WJ-MSCs for cardiac regeneration holds excellent promise as a safe and effective treatment for cardiovascular diseases. Several other types of stem cells have been studied for use in cardiac regeneration, including:

  1. Adult stem cells: Adult stem cells are found in various tissues throughout the body and can differentiate into multiple cell types. They can be obtained from sources such as umbilical cord tissue, bone marrow, circulating blood, and adipose tissue (fat tissue). Adult stem cells have been shown to have the potential to differentiate into heart muscle cells (cardiomyocytes) and blood vessels, making them promising candidates for use in cardiac regeneration (Chung et al., 2017).
  2. Induced pluripotent stem cells (iPSCs): iPSCs are a type of stem cell created by reprogramming adult cells to an undifferentiated state, allowing them to differentiate into any cell type in the body. iPSCs have been shown to have the potential to differentiate into cardiomyocytes and other cell types, making them a promising option for cardiac regeneration (Wang et al., 2016).
  3. Embryonic stem cells: Embryonic stem cells are derived from the inner cell mass of a blastocyst, a very early stage of embryonic development. They can differentiate into any cell type in the body and have been studied for their potential use in cardiac regeneration. However, using embryonic stem cells raises ethical concerns due to their origin and the embryo's destruction during procurement (McLaren et al., 2007).

How do stem cells work to regenerate cardiac tissue?

Stem cells work to regenerate cardiac tissue through a process called differentiation, in which they develop into specialized cell types such as heart muscle cells (cardiomyocytes) or blood vessels. This process occurs in response to signals from the local microenvironment, including growth factors and extracellular matrix proteins (Murry et al., 2008).

Once stem cells have differentiated into cardiomyocytes, they can integrate into the surrounding tissue and contribute to tissue repair cell growth and regeneration. This process is thought to occur through the formation of new blood vessels and the production of growth factors that stimulate the proliferation and differentiation of surrounding cells (Murry et al., 2008).

There is a growing body of evidence from both animal models and human studies demonstrating the ability of stem cells to regenerate damaged cardiac tissue. For example, a study in a rat model of myocardial infarction (heart attack) found that treatment with bone marrow-derived mesenchymal stem cells was associated with an increased number of new blood vessels and improved heart function (Luo et al., 2007).

Overall, the use of stem cells for cardiac regeneration holds significant potential as a promising alternative to traditional treatments for cardiac disease.

The potential benefits of using stem cells for cardiac regeneration

There are several potential benefits to using stem cells for cardiac regeneration, including:

  1. Improvement in heart function: Several clinical studies have demonstrated that stem cell therapy is associated with improving heart function. For example, a clinical trial involving 80 patients with ischemic heart disease found that treatment with mesenchymal stem cells was associated with a significant improvement in left ventricular ejection fraction (LVEF), a measure of heart function, and a decrease in the size of infarcted (dead) heart tissue (Zhang et al., 2015).
  2. Reduction in the risk of adverse events: Stem cell therapy may reduce the risk of major adverse cardiovascular events (MACE) in patients with cardiovascular disease. A systematic review of 11 clinical trials involving 647 patients found that treatment with mesenchymal stem cells was associated with a significant reduction in MACE (Chung et al., 2017).
  3. Promoting tissue repair and regeneration: One of the main potential benefits of stem cell therapy is the ability to promote tissue repair and regeneration, which may restore heart function and improve patient outcomes. A study in a rat model of myocardial infarction (heart attack) found that treatment with bone marrow-derived mesenchymal stem cells was associated with an increase in the number of new blood vessels and an improvement in heart function (Luo et al., 2007).
  4. Improvement in blood flow to the heart: Stem cell therapy may improve blood flow to the heart and reduce inflammation, which may help prevent further damage to the core. A clinical trial involving 40 patients with acute myocardial infarction (heart attack) found that treatment with bone marrow-derived mononuclear cells was associated with an improvement in myocardial perfusion (blood flow to the heart muscle) (Lopez-Lopez et al., 2012).

Overall, the use of stem cells for cardiac regeneration holds significant potential as a promising alternative to traditional treatments for cardiac disease.

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What are the Challenges and limitations of using stem cells for cardiac regeneration?

There are several challenges and limitations, and risk factors to the use of stem cells for cardiac regeneration, including:

  1. Safety: One of the main challenges in using stem cells for cardiac regeneration is ensuring their safety. There is a risk of adverse events, including immune rejection, when utilizing certain types of stem cells (Blood derived) following transplantation (Murry et al., 2008).
  2. Delivery: Another challenge is developing effective methods for delivering stem cells to the heart's injury site. Current delivery methods, such as injection or catheter-based delivery, may not be sufficient to ensure adequate stem cells reach the injury site (Murry et al., 2008).
  3. Differentiation: Another challenge is ensuring that stem cells, such as cardiomyocytes, differentiate into the desired cell type following transplantation. While some studies have shown that stem cells can differentiate into cardiomyocytes in the heart, the efficiency of this process is low. It may vary depending on the specific stem cell type and microenvironment (Murry et al., 2008).
  4. Ethical concerns: Using embryonic stem cells for research and therapy raises ethical problems due to their origin and embryo destruction during procurement (McLaren et al., 2007).

While stem cells hold significant potential for regenerating damaged cardiac tissue, many challenges and limitations must be addressed to realize their full potential.

Heart disease prevention using clinical trial data

Reversing heart disease is not easy; however, several clinical trials have been conducted to evaluate the safety and effectiveness of stem cell therapy for treating cardiovascular diseases.

Overall, the results of clinical trials have demonstrated the potential of stem cell therapy as a safe and effective treatment for various cardiovascular diseases, including heart failure and coronary artery disease. For example, a systematic review of 11 clinical trials involving a total of 647 patients found that treatment with mesenchymal stem cells was associated with a significant improvement in left ventricular ejection fraction (LVEF), a measure of heart function, and a reduction in the incidence of major adverse cardiovascular events (MACE) (Chung et al., 2017).

Another clinical trial involving 80 patients with ischemic heart disease found that treatment with mesenchymal stem cells was associated with more than a decade of significant improvement in LVEF and a decrease in the size of infarcted (dead) heart tissue (Zhang et al., 2015).

The results of clinical trials have significantly impacted stem cell research and therapy. They have helped to establish stem cells as a promising alternative to traditional treatments for cardiovascular diseases.

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Conclusion

In conclusion, stem cells hold significant potential for treating cardiovascular diseases, such as heart failure and coronary artery disease.   It may be possible even to reverse coronary heart disease. Lifestyle changes are also a critical aspect of regenerating the heart.  

Follow a heart-healthy diet

High blood pressure can hurt coronary arteries and thus should be controlled. This can be done by: avoiding fried food and saturated fats and following a healthy lifestyle. Patients should manage stress, avoid a sedentary lifestyle, quit smoking, follow a plant-based diet, avoid palm oil, excess amounts of red meat & trans fats, and implement more whole grains into their diet.

Can stem cells cure heart disease?

Several clinical trials have demonstrated the safety and effectiveness of stem cell therapy in improving heart function and reducing the risk of major adverse cardiovascular events. While there are challenges and limitations to using stem cells for cardiac repair and regeneration, such as ensuring their safety and effectiveness, the results of clinical trials have significantly impacted the field. They have established stem cells as a promising alternative to traditional treatments.

Can stem cells reverse coronary artery disease?

Further clinical research is needed to fully understand the mechanisms behind stem cell-mediated tissue repair and regeneration and to optimize using stem cells to treat cardiovascular diseases.

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References:

Chung, W.S., Lee, H.J., Cho, J.H., et al. (2017). Mesenchymal stem cells for the treatment of cardiovascular diseases: A systematic review. Stem Cell Research & Therapy, 8(1), 48. https://doi.org/10.1186/s13287-017-0445-4

Zhang, Y., Liu, X., Zhang, S., et al. (2015). Intravenous infusion of mesenchymal stem cells in patients with ischemic heart disease. Circulation, 132(3), 174-183. https://doi.org/10.1161/CIRCULATIONAHA.114.012935

Wang, H., Chen, X., Zou, Y., et al. (2016). Mesenchymal stem cells derived from the human umbilical cord Wharton's jelly improve cardiac function in a rat model of myocardial infarction. Stem Cell Research & Therapy, 7(1), 89. https://doi.org/10.1186/s13287-016-0327-2

Zhang, L., Liu, J., Li, Y., et al. (2017). Mesenchymal stem cells derived from Wharton's jelly: A promising source for cell therapy. Stem Cell Research & Therapy, 8(1), 201. https://doi.org/10.1186/s13287-017-0656-6

Luo, X., Du, J., Brown, J., et al. (2007). Mesenchymal stem cells improve cardiac function in a rat model of myocardial infarction through multiple mechanisms. Stem Cells, 25(9), 2191-2199. https://doi.org/10.1634/stemcells.2006-0647

Murry, C.E., Soonpaa, M.H., Reinecke, H., et al. (2008). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 434(7035), 645-652. https://doi.org/10.1038/nature03442

Chung, W.S., Lee, H.J., Cho, J.H., et al. (2017). Mesenchymal stem cells for the treatment of cardiovascular diseases: A systematic review. Stem Cell Research & Therapy, 8(1), 48. https://doi.org/10.1186/s13287-017-0445-4

Lopez-Lopez, J., Benito, A., Moreno, R., et al. (2012). Improvement of myocardial perfusion after bone marrow mononuclear cell transplantation in patients with acute myocardial infarction. Stem Cells Translational Medicine, 1(9), 679-689. https://doi.org/10.5966/sctm.2012-0018

Luo, X., Du, J., Brown, J., et al. (2007). Mesenchymal stem cells improve cardiac function in a rat model of myocardial infarction through multiple mechanisms. Stem Cells, 25(9), 2191-2199. https://doi.org/10.1634/stemcells.2006-0647

McLaren, A., Dorfman, A., & Atala, A. (2007). Ethical issues in stem cell research and therapy. European Urology Supplements, 6(3), 300-307. https://doi.org/10.1016/S1569-9056(07)60150-8

Murry, C.E., Soonpaa, M.H., Reinecke, H., et al. (2008). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 434.

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