The novel coronavirus (SARS-CoV-2) has affected over 28 million people across the United States, according to the CDC. At the present time, there is no effective cure for COVID-19 (2, 3). While widely publicized drugs like remdesivir and chloroquine have shown promising results in treating symptoms of COVID-19 in some instances, other studies have found that they make no significant difference (3). The lack of headway in finding an effective treatment is leading scientists across the world to turn to alternative regenerative therapies. The use of stem cells to treat COVID-19, including mesenchymal cells, is now being studied in over 34 clinical trials across the world (4).
Difficulties in Finding a Treatment for COVID-19
Before diving into how mesenchymal cells may be a promising therapy for treating COVID-19, it is helpful to understand what makes treating the disease so difficult in the first place. Lung diseases have long been a source of study for clinicians, especially those caused by viral infections or those that lead to acute respiratory distress syndrome (ARDS) (2, 5). ARDS occurs due to an extreme pro-inflammatory response that creates a cytokine storm, often causing lung damage, respiratory failure, inflammation, and damage to the cardiovascular system (4). Other disease-causing viruses, such as SARS-CoV-1, MERS-CoV (Middle East Respiratory Syndrome), and H7N9 (avian flu) can cause ARDS or ARDS-like effects, just as the current SARS-CoV-2 does (2, 6). Treatments of choice up to this point have been antibiotic therapy, ventilation, and anti-inflammatory pharmaceuticals, though these have all presented low success rates (5). Because these treatments do not meet efficacy standards, research to find other potential cures for respiratory diseases via modalities such as cell therapies has been underway for years (2, 5).
What are Cell Therapies?
There are a variety of cell therapies, including many different kinds of ethically-donated stem and progenitor cells (5). Though cell therapies generally show potential for repairing tissue damage and promoting tissue regeneration for a variety of ailments, mesenchymal stromal/stem cell (MSC) therapies have risen to the forefront of study, specifically for the treatment of lung diseases such as COVID-19 (4, 5). Even so, it is important to note that while previous clinical trials have determined cell therapies to be safe, any claims about stem cells have not been approved by the FDA.
Interestingly, while the debate continues as to whether mesenchymal cells can actually be classified as stem cells, they undoubtedly show the same characteristics that are traditionally attributed to stem cells in clinical trials (7). MSCs are naturally found in bone marrow, fat, and other tissues and, when isolated and introduced into the body, make their way to sites of damage or inflammation in the body (7). While the exact interactions of MSCs with their surroundings on the cellular level are still being determined, the effects on a variety of conditions have been shown as largely positive long-term (2, 3, 4, 5, 7).
In the instances that mesenchymal cells have been specifically studied as a treatment for lung-related diseases, ARDS, and even for COVID-19 specifically, MSCs show the ability to work with the body’s natural processes. In this way, they have the ability to address and prevent immune-mediated effects, restore damaged tissue, reduce inflammation, and more (3, 4).
Effects of COVID-19 on the Immune System
What has been determined about COVID-19 so far tells us that the body’s immune system can respond quickly and very severely. In its overreaction, the immune system can send too many destructive, antigen-destroying cells such as macrophages and neutrophils to attack (4, 5). This leads to an over-production of pro-inflammatory cytokine proteins, which can create a generally dysregulated inflammatory response (4, 5). As a result of this dysregulation, the immune system may signal the body to produce more macrophages, leading to an even greater imbalance over time (4, 5). Many clinicians believe this process of respiratory dysregulation can directly contribute to the lung damage and respiratory failure that is at the root of ARDS, many viral lung-based diseases, and importantly, severe cases of COVID-19 (4).
How MSCs Can Work to Combat Infection and Damage
When mesenchymal cells are introduced into a body that is experiencing the above immune-mediated effects, they travel to the damaged and inflamed areas of the lungs. Once there, they begin to affect the surrounding tissues and cells in a few key ways. First, they start to secrete growth stimulants, such as trophic factors, which help damaged tissue to repair and regenerate itself (4, 8). Simultaneously, they influence the surrounding cells by secreting anti-inflammatory molecules. These molecules not only reduce inflammation so that the newly stimulated growth and regeneration aren’t inhibited, but also allow cells to live longer (4, 8). MSCs are thought to potentially work to regulate the immune system’s inflammatory response as well (4, 8). These factors altogether can also defend against the cytokine storms that can sharply increase inflammation and cause greater damage (2). Lastly, these Mesenchymal cells aid by bringing antimicrobial protection and viral resistance to the cells and tissue they reside next to (4).
Results of MSC Use on Lung-Related Diseases
These effects have been shown in the existing studies that have used MSC therapies to treat those with lung diseases. In cases of pneumonia, mesenchymal cell therapy has been proven to reduce lung inflammation, reduce alveolar fluid buildup, and improve lung injury (3, 8). Similar results are achieved when treating influenza patients with severe symptoms, including the H7N9 avian flu (2, 8). In fact, one study done on patients experiencing severe H7N9 infections indicates significant results come from using MSC therapy. There were little to no adverse events or effects 5 years post-treatment, and mortality was significantly decreased for those who elected to receive MSC treatment over standard antiviral treatment (a 17.6% mortality rate vs 54.5%) (2).
Given these results, some physicians have offered MSC therapy to patients experiencing serious effects from COVID-19. Although the sample size is incredibly small, these patients have shown improved clinical symptoms with no side effects as early as two days after receiving the MSC injection (3). Lung tissue regeneration increased, pro-inflammatory cells decreased, and overall microenvironment inflammation and inflammatory response were better regulated (3, 9).
Potential Issues and Areas of Study
It is important to note again that even those these results are positive, this sample size is far too small to determine that cell therapies are ready for use to treat COVID-19 or other diseases that target the respiratory system. While studies so far have been consistent in reporting that MSCs stay in the lungs for only a short time, more studies with higher quality equipment are necessary to determine this to be true (8). If mesenchymal cells remain present in damaged areas long-term, they could eventually become problematic. Though it has not occurred in studies, mesenchymal cells do have the potential to promote inflammation and tumor growth. Thus, it is important to understand what conditions could cause MSCs to behave this way in order to not potentially inflict greater damage to tissues (5, 8). Additionally, very high doses of MSCs have aggravated lung damage, which can potentially lead to respiratory and cardiac arrest (8). Lastly, not all MSCs are equally effective, so practical factors such as mesenchymal cell type, cell abundance and supply, and storage temperature and transportation are all hurdles that must be taken into account (5, 8).
Overall, many studies and physicians do see great potential for cell therapies to treat respiratory disorders and diseases, including COVID-19. While these therapies are not currently being used for COVID-19, many physicians, including those of us here at the Temecula Center for Integrative Medicine, have been using stem cell therapies for years. This regenerative therapy, along with Pulsed Electromagnetic and Platelet Rich Plasma therapies, has brought great benefit to many patients who are seeking healing. If you have any questions about COVID-19, regenerative therapies, or any other aspect of your family’s health, please reach out to us! We would love to schedule a consultation with you to discuss any concerns or questions you may have.
Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.
Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functio