Myocarditis Treatment With Stem Cells

What is Myocarditis?

Myocarditis is an inflammatory condition of the heart muscle that can cause damage to the heart and impair its ability to pump blood effectively. It is a relatively rare condition, but it can be serious if not treated promptly. Patients with acute myocarditis often experience symptoms such as fatigue, shortness of breath, chest pain, palpitations and irregular heartbeat. If left untreated, active myocarditis can culminate in clinical manifestation of serious sequelae, including dilated cardiomyopathy, congestive heart failure, severe heart failure, heart attack (cardiac arrest), and sadly, even sudden death (cardiac death). 

How is myocarditis diagnosed?

The diagnosis of myocarditis requires a thorough evaluation, including a systematic review of clinical features, various types of cardiac imaging, and a tissue diagnosis. 

Myocarditis is typically diagnosed with a review of medical history, physical examination, collating a differential diagnosis by evaluating cardiovascular symptoms, onset of symptoms, symptom duration. Various diagnostic tests pre and post onset of symptoms are further performed.

Blood tests can be used to check for signs of myocardial inflammation, chronic inflammation or infection, such as elevated levels of white blood cells, C-reactive protein, or cardiac enzymes (troponin, creatine kinase, myoglobin).

An ECG records the electrical activity of your heart and can detect various forms of coronary syndrome, abnormal heart rhythms, damage to the heart muscle, cardiac dysfunction (ventricular function, ventricular dysfunction, ventricular tachycardia, ventricular fibrillation, systolic function, systolic dysfunction, pericardial effusion, and any dilated cardiomyopathy phenotype).

A cardiac MRI (magnetic resonance imaging) is a more detailed cardiac imaging diagnostic tool and can provide information about the size and function of the heart, as well as any signs of inflammation or damage to the heart muscle.

Coronary angiography and tissue diagnosis from myocardial tissue (endomyocardial biopsy) are also ordered. In fact, a biopsy sample is considered the most precise diagnostic accuracy. Biopsy-proven myocarditis is the gold standard.

In case of infectious or viral myocarditis (eosinophilic myocarditis, lymphocytic myocarditis, fulminant myocarditis), antibody tests and viral genome analysis is added in stable patients to identify the cause of the  onset of symptoms and guide treatment strategy. 

What are the conventional treatments for Myocarditis?

Conventional medical treatment options for myocarditis involve a combination of medications and lifestyle modifications.

Usual care of acute myocarditis and cardiomyopathy involves acute phase drugs, such as intravenous immunoglobulin, cyclophosphomide and rituximab. Immunosuppressive therapy with anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids are further used to reduce inflammation and relieve symptoms. Immune checkpoint inhibitors and immunosuppressive treatment may be prescribed if inflammatory disease process is identified.

In patients with virus driven cardiovascular symptoms, antiviral therapy is used. Chronic virus conditions such as Epstein-Barr virus or Human Herpesvirus can present as a cardiac clinical syndrome. 

Diuretics may also be used to reduce fluid buildup in the body, while beta-blockers or calcium channel blockers may be used to help the heart pump more effectively. In severe cases, patients may require hospitalization and supportive care, such as oxygen therapy or mechanical ventilation.

While these treatments can be effective in managing symptoms and preventing complications, they do not address the underlying cause of the condition and myocardial recovery can be complex. The bridge to recovery can usually be build with functional and regenerative approaches. 

What are functional treatments for myocarditis?

From a functional medicine perspective, myocarditis occurs when the heart muscle succumbs to tissue inflammation, an autoimmune disease process which can weaken the heart and reduce its ability to pump blood. Health care providers of functional medicine recognize that myocarditis can have a variety of underlying causes, such as viral or bacterial infections, autoimmune disorders, or environmental toxins. By identifying and addressing these root causes, functional medicine aims to not only reduce inflammation in the heart but also remove cardiovascular toxicities to improve overall health and prevent the condition from recurring. Functional medicine therapy for myocarditis may involve a combination of dietary changes, dietary changes, targeted supplementation, and lifestyle modifications, such as stress reduction and exercise. For example, for autoimmune myocarditis, anti-inflammatory diet, immune-regulating supplements and therapies may be prescribed. Other approaches may include addressing underlying infections, such as Lyme disease or viral infections, that may be contributing to the condition. 

What are regenerative treatments for myocarditis?

Regenerative medicine is an emerging field that seeks to use the body's natural healing processes to repair damaged tissue. In the context of Myocarditis, this may involve the use of stem cells or other cellular therapies to stimulate repair and growth of new heart tissue and improve cardiac function. Unlike conventional medicine, which often focuses on managing symptoms, regenerative medicine aims to restore the damaged tissue to its healthy state. One promising approach involves the use of pluripotent stem cells, which have the ability to signal repair in all 220+ tissue types of the body, including the heart. Other cellular therapies may involve the use of cardiac progenitor cells, which have a more limited ability to differentiate into heart cells, or mesenchymal stem cells, which can help modulate the immune response and reduce inflammation. While these therapies are still in the early stages of development, they hold promise for restoring normal cardiac function in patients with Myocarditis.

What are pluripotent stem cells? 

Pluripotent stem cells are a type of stem cell that have the ability to differentiate into any type of cell in the body and signal repair in all tissue types of the body. There are three types of pluripotent stem cells: 1. embryonic pluripotent stem cells (ePSCs), which are derived from a blastocyst, 2. induced pluripotent stem cells (iPSCs), which are generated in a laboratory by reprogramming adult cells with Yamanaka factors, and 3. nuclear-mitochondrial transfer pluripotent stem cells (nmtPSCs), which are derived by nuclear and mitochondrial transfer and are considered the gold standard of autologous pluripotent stem cells.   

Embryonic Pluripotent Stem Cells (ePSC)

Embryonic stem cells are derived from a group of cells known as the inner cell mass, which is obtained from a tissue line grown from the blastocyst. The blastocyst, formed five days after fertilization, splits into two layers: the outer cell mass, which develops into the placenta, and the inner cell mass, which contains all the necessary information to grow and repair all tissues in the body. While a stem cell line grown from the inner cell mass cannot develop into a fully-formed body, it has the potential to repair, reprogram and regenerate any of the 220+ tissue types in the body. This is what makes embryonic stem cells so effective in reaching and repairing various tissues, including the heart.

Induced Pluripotent Stem Cells (iPSC)

Induced pluripotent stem cells (iPSC) are stem cells that are similar to embryonic stem cells and are created in a laboratory by reprogramming adult somatic cells, typically from the skin. The potential of iPSCs to differentiate into any tissue type has led to the development of stem cell therapies that could provide an unlimited supply of various human somatic cells for therapeutic purposes. This includes, but is not limited to cardiac cells. The potential of human induced pluripotent stem cells (iPSCs), also known as undifferentiated iPSCs, lies in their ability to serve as a starting material for autologous cell therapies. They are not available clinically just yet. 

Nuclear and Mitochondrial Transfer Pluripotent Stem Cells (nmtPSC)

Stemaid International Laboratories uses a unique Nuclear-Mitochondrial Transfer cloning technique that differs significantly from iPSC induction. This method does not require retroviral delivery and produces pluripotent embryonic stem cells that exactly match a patient's nuclear and mitochondrial DNA from their somatic cells, such as skin cells.

Somatic cell nuclear transfer technology, which has been available for several decades, is known as somatic cell nuclear transfer (SCNT), and the resulting cells are referred to as somatic cell transfer-derived embryonic stem cells (SCNT-ESC). Although the embryonic stem cells produced by this method are autologous with regard to the nuclear DNA, they still contain mitochondrial DNA from the donor. The issue with this approach is that the presence of foreign maternal mitochondrial DNA in autologous embryonic cells can trigger immunorejection, making engraftment impossible.

From a clinical perspective, immunorejection of foreign DNA is a natural occurrence in biology, and cell fate is not the most critical determinant since the transient signaling profile of exosomes released by the stem cells prior to differentiation is more important in regenerative therapy. The stem cell secretome's content, including miRNA, mRNA, and peptides, is thought to be the most crucial therapeutic element in orthopedic, aesthetic, and regenerative medicine. However, if the goal is to replenish the depleted stem cell stores that occur during chronic illness and aging, engraftment and integration are desired. The aim is to ensure that the autologous stem cells remain in the body, replenish the stores, and continue signaling repair, rejuvenation, and reprogramming in the long term. As a result, Stemaid's scientists have created a unique cloning method that ensures that embryonic stem cells are autologous in both nuclear and mitochondrial content.

Why are Pluripotent Stem Cells considered as a potential treatment for Myocarditis?

Efficacy of stem cells and exosomes depends on their signaling profile and secretome content. Mesenchymal stem cells (derived from umbilical cord blood, placenta, fat transfer, bone marrow) are the most widely studied stem cell types in systematic review of myocarditis literature. Pluripotent stem cells and their unique exosomes are especially key in such regenerative therapeutic approaches in cardiac function, and also exhibit positive benefit in the literature. Pluripotent stem cells and exosomes contain transcription factors, proteins, lipids, nucleic acids, mRNA, miRNA, long noncoding RNA, circular RNA and other molecules that have multitude of benefits on the human body. The contents are nuclear/mitochondrial DNA reparative, neurotrophic, angiogenic, anti-fibrotic, telomere elongating, pro-growth. They are involved in immune regulation and tissue repair. They have immunomodulatory and suppressive effects on inflammatory immune cells and cytokines, and help repair or regulate disease progression in chronic illnesses, including autoimmune disease and cardiovascular disease. Pluripotent exosomes contain cellular reprogramming factors, Yamanaka factors, that add an extra benefit of biological age reversal in human tissues. Potential of exosomes in treating chronic degenerative diseases is vast, including for myocarditis. To learn more about the therapeutic content of pluripotent exosomes, Plurisomes, see our article "A Guide to Exosome Therapy"

All conditions of the heart, including acute myocarditis, and other active myocarditis such as autoimmune myocarditis, lymphocytic myocarditis, eosinophilic myocarditis, fulminant myocarditis, viral myocarditis, ICI-associated myocarditis, even myocarditis in children, can benefit from stem cell derived signaling profile. All cardiovascular clinical syndrome types can benefit, including congestive heart failure, arthythmias, coronary syndrome types and cardiac autoimmune disorders. The acellular portion of the stem cells is used in immunocompromised patients, such as post cardia transplantation, Outcome in patients depends on reparative vitality, severity of conditions and duration of treatment. Recovery from myocarditis may require weeks and months of treatment. 

A Special Note: Myocarditis in young populations

Cardiovascular disorders are very rare in children. For instance, according to the American Heart Association, only 6% of all giant cell myocarditis in the United States occur in pediatric patients. Recently however, acute myocarditis has been showing up in literature, in clinical settings and even in intensive care units, as a potential rare side effect of the COVID-19 virus and certain COVID-19 vaccines in pediatric patients. The Centers for Disease Control and Prevention (CDC) in the United States has reported cases of myocarditis in children and young adults after receiving Covid-19 vaccines, particularly after the second dose. While the risk is still considered to be low, with the majority of cases being mild and resolving quickly, there is growing concern about the potential link between myocarditis and sudden cardiac events in young populations and in competitive sports. It is important for parents, coaches, and healthcare providers to be aware of the potential risk and to promptly evaluate any concerning symptoms such as chest pain, shortness of breath, or palpitations. To learn about how early pediatric patients can start pluripotent stem cell therapy, visit our article "How early should one start pluripotent stem cell therapy".