The immunomodulatory properties of hu-MSCs may prove valuable in the treatment of severe COVID-19 cases
Mesenchymal stem cells (aka MSCs) aren’t new. Scientists first discovered and isolated MSCs 30 years ago more, and since then more than 5,000 articles focused on MSCs, ranging from basic science to clinical applications, have been published. In the last 10 years, MSCs have largely been studied in several clinical trials for their immunomodulatory and anti-inflammatory properties, rather than tissue regeneration.
With the COVID-19 pandemic, and inflammation being the main cause of death in patients whose symptoms progressed into ARDS, many scientists are asking, can MSCs help treat patients with COVID-19?
Due to their strong immunomodulatory capabilities and anti-inflammatory effects, they in fact may prove helpful in treating COVID-19. MSCs and their ability to modulate the immune system’s response to certain instigators, and regulate inflammatory cytokines, look promising in helping manage this disease.
COVID-19 has spread unabatedly across the globe, and the United States leading to a national emergency with serious health care and economic impact. The virus has sent the many countries into a recession with disrupted lifestyles not seen in recent history. It is a serious illness that is responsible for countless global deaths. While there are many treatments being studied for managing this disease, MSCs may be a viable COVID-19 treatment option.
A current search on Clinicaltrials.gov shows at least 60 registered clinical trials using MSC as a therapeutic treatment. The source of MSC varies from bone marrow, Wharton’s Jelly, and umbilical cord tissue. The trials are at various stages, ranging from recruitment to completed. The clinical trials are taking place at leading hospitals at major cities across the world. Just in this search inquiry, it shows that to develop an MSC therapy for this new coronavirus requires a global effort.
The theory of using MSCs for COVID-19 treatment is much more than immune modulation. Over the past year, trials have noticed that treating severe COVID-19 patients with hUC-MSCs had various beneficial effects. A study by Feng, et al, showed gene expression profiling on hUC-MSCs are deficient in viral target proteins, such as ACE2 and TMPRSS2 and are thus, resistant to COVID-19 infection. This is a remarkable finding and means that freshly infused therapeutic MSCs are not targets for the virus and will be able to function without losing their immunomodulatory properties.
In addition to their immunomodulatory properties and differentiation abilities, hUC-MSCs can reduce lung tissue injury by restricting the cytokine storm. Mortality in COVID-19 patients has been linked to the presence of the so-called “cytokine storm” induced by the virus. Normal anti-viral immune responses by the body requires the activation of the inflammatory pathways of the immune system. This is a standard, normally protective, reaction to pathogenic invaders of all types. However, aberrant, or exaggerated response of the host’s immune system can cause severe disease if it remains uncontrolled for a prolonged period. COVID-19-infected patients with elevated and sustained levels of IL-1β, IL-7, IL-8, IL-9, IL-10, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1A, MIP1-B, PDGF, TNF-α, and VEGF are considered to be suffering from the cytokine storm.
The key mechanism for using MSCs in COVID-19 clinical trials is their ability reduce levels of TNF-α, IL-1β, and IL-6 by releasing hepatocyte growth factor (HGF), prostaglandin-E2 (PGE2), lipoxin A4 (LXA4), and TNF-stimulated gene 6 (TSG-6), thereby suppressing the systemic inflammatory response of overactive immune cells. Other benefits from MSC have been observed to include upregulation in the expression of genes linked to cell proliferation, survival, glycolysis, and angiogenesis under hypoxic conditions. MSCs are known to have the ability to home to damaged tissues and then interact with various resident cells to provide local trophic support. Taken all together, hUC-MSC applications in combination with other basic treatments may be a valuable option for treating patients suffering from COVID-19.
In general, there is an advantage to initiating MSC transplantation at an earlier stage of the disease to enable the positive immune regulatory effect of MSCs on the destructive cytokine storm. Many of the ongoing clinical trials are small scale and with patients at various stages of infection. Over the next few months, the clinical and scientific community will have better understandings of MSC transplantation for responsive COVID-19 patients.