Stem Cell and Regenerative Medicine for COVID-19: Opportunities and Challenges

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In less than 10 months, the SARS-CoV-2 coronavirus has spread rapidly across the globe, infecting more than 81 million people and killing nearly 2 million people. The explosive spread of the virus and the high death rate spurred global public health restrictions and sped off early groundwork on the nature and cure of the disease, but the virus continues to sweep through the world in many waves, infecting and killing thousands of people daily.

Findings from global research on therapies for the novel coronavirus have yielded positive results only for a handful of drugs. In November, the US Food and Drug Administration issued an emergency use authorization (EUA) for the drug Baricitinib, in combination with the earlier approved antiviral drug remdesivir, for the treatment of suspected or laboratory-confirmed COVID-19 in hospitalized adult and children aged two years and older that require respiratory support.

Although both drugs were found to reduce recovery time and reverse complications of the disease, COVID-19 still has a high death rate, leading experts to explore other therapeutic options to address the fatal disease. One such option is regenerative medicine, which uses biological treatments to modify the immune system and rejuvenate dying tissues.

Potential Benefits of Stem Cell Therapy for COVID-19 Treatment

Scientists are currently investigating the role of mesenchymal stem cells (MSCs) — which are unspecialized cells in the body that can divide into different cell types — in reversing tissue destruction and multiple organ failure seen in COVID-19 and lowering the risk of death from the disease. Although there are different types of stem cells, MSCs are the special focus for stem cell-based therapies because of their regenerative and immune-modifying potential.

COVID-19 causes death through several pathways, including immune-mediated multiple organ failure from septic shock and widespread formation of blood clots. Researchers say MSCs can reprogram the immune cells to prevent cytokine storm — the inflammatory response that sets off these complications in COVID-19. Further, research shows that MSCs can improve lung function by protecting it from harmful, inflammatory substances.

More than 60 clinical trials are currently underway worldwide, investigating the role of this new biological therapy in the treatment of COVID-19. Many countries, including the US, Brazil, UK, France, Germany, and Spain have proposed stem cell therapies for COVID-19. At least two of the trials currently running have reported the safety and efficacy of MSC-based treatment for COVID-19.

The first study conducted in China showed that all seven confirmed COVID-19 patients who participated experienced improved clinical outcomes after receiving a single dose of an MSC infusion. Five of the participants had severe COVID-19 disease, with one receiving treatment in an intensive care unit.

The second study involved a larger sample size - 31 patients, all of whom experienced improved lung function and reduced cytokine storm, which triggers widespread inflammation and multiple organ failure. Both studies reported no adverse events, such as allergic reactions or secondary infections, following MSC administration.

Also, findings from a trial at the Abu Dhabi Stem Cell Centre (ADSCC) revealed that patients who received stem cell treatment, called UAECell19, were 3.1 times more likely to recover within seven days than those treated with conventional therapy. The study further noted that 67 percent of those who received stem cell therapy recovered fully.

Although positive results are still limited, several stem cell biotechs, including Hope Biosciences and Athersys, are joining forces to accelerate research and development of MSC products as therapeutic solutions for COVID-19.

Potential Challenges of Stem Cell Treatment for COVID-19

While MSC-based stem cell therapy may be a viable therapeutic option for COVID-19, it may be fraught with several controversies and potential challenges.

First, while the results have been promising, data is still insufficient to prove that they are safe and effective for the treatment of COVID-19. The studies that have also been done largely involved small sample sizes without appropriate controls. The treated groups in these trials were also treated with conventional antiviral therapy, which raises questions of whether the improved clinical outcomes were due to the stem cell treatments or other medications. Multicenter studies with proper randomization and a larger sample size are therefore needed to evaluate the safety and efficacy of stem cell therapy for COVID-19.

Another challenge that may impede stem cell treatment for COVID-19 is the delay in producing a substantial number of stem cells required for therapeutic purposes. It takes a considerable amount of time to produce a large number of stem cells, and in the context of the current COVID-19 emergency, that may be a challenge. Laboratory expansion of stem cells to rapidly produce hundreds of millions of cells to reach a therapeutic dose is not only time consuming but may also reduce the potential of the resulting cells.

Furthermore, harvested MSCs must be processed in Good Manufacturing Practice (GMP)-compliant facilities to produce clinical-grade stem cells; this may be a major challenge for several countries, especially the developing nations. Given that stem cells are harvested from tissue sources, including placenta, cord blood, and bone marrow, selecting the right donors to provide the required number of cells during the pandemic may be challenging.

For these reasons, stem cell-based treatments for COVID-19 may be very expensive. Even if federal governments initiate programs to procure and distribute stem cell treatments to COVID-19 patients, it would only cover a small patient number.

Experts have also raised concerns about a greater risk of viral infections in immunocompromised COVID-19 patients receiving stem cell treatment. MSCs have an immunosuppressive potential, which could worsen clinical outcomes for such patients.

Further, there is a growing body of evidence that suggests that MSCs may potentiate drug resistance. In cancer patients receiving MSC-based therapy, drug resistance is a common finding. This results from an MSC-induced tumor environment that makes cancer cells impermeable to drugs and, thus, insensitive to treatment. This phenomenon could also potentially reduce treatment efficacy.

Addressing these challenges could open a world of opportunities for stem cell treatment of COVID-19 and many other diseases.

Conclusion

Stem cell therapy offers a promising treatment approach to COVID-19 due to their immunomodulatory and regenerative properties. Currently, MSC-based therapies are being used as an emergency protocol for treating the cytokine storm in critically ill COVID-19 patients, however, with more research and data, the treatment could be expanded to become a standard treatment for moderate to severe disease, and even as a preventive treatment for those at risk.