A number of clinical trials are currently underway investigating the potential use of Mesenchymal
Stem Cells (MSCs) in the treatment of COVID-19. While the research done to date has shown promising results, it must be remembered that these clinical trials have yet to transition to proven therapies. Nevertheless, we feel it important to share the status of current trials investigating the use of MSC’s for COVID-19 treatment and why scientists believe this approach may be valuable.
Studies have shown that the SARS-COV2 virus enters host cells by recognising and binding to the angiotensin-converting enzyme-2 (ACE2); this is facilitated by its spike protein. In a separate study, it was further shown that entry of the virus into host cells also requires TMRRSS2, a cellular protease. The ACE2 receptor is widely distributed on the surface of human cells, and in particular on capillary epithelium and alveolar type 2 (AT2) cells; furthermore, AT2 cells largely express TMPRSS2. In addition to the cells of the lung, AEC2 is also widely expressed on human epithelial tissues on the heart, liver, kidney and digestive organs as well as on most endothelial cells and smooth muscle cells. Therefore, once the virus enters the blood stream it can spread widely around many organs in the body. For this reason, scientists believe that immune-based therapy may help in the treatment of COVID-19 infected patients.
Severe cases of the virus have been characterised by an over-stimulation of the immune system, as it attempts to kill the virus, leading to a so-called a cytokine storm. A cytokine storm, in simple terms, is an overreaction of the body’s immune system. It contributes significantly to the potentially fatal effects of COVID-19, causing oedema in the lungs, acute respiratory distress, acute cardiac injury, organ damage and secondary infections, which may lead to death. Therefore, avoiding or reducing this cytokine storm is key in the treatment of COVID-19 infected individuals; and immunological therapy with just one or two immune factors, may not be enough to counteract the cytokine storm.
MSCs have previously been shown to possess both a high regenerative potential as well as anti-inflammatory properties and a powerful immunomodulatory ability. MSCs have also been shown to be ACE2 negative and TMPRSS2 negative, thereby possessing a natural immunity to COVID-19. For these reasons, MSC therapy is being explored to determine its efficacy in preventing or reducing the cytokine storm. Effectiveness and safety of MSCs has been explored and documented in many clinical trials to date; in particular their effectiveness with immune-mediated inflammatory diseases have been noted. The immunomodulating effects of MSCs is related to their ability to secrete a range of cytokines and interact directly with immune cells. MSC therapy could therefore inhibit the overactivation of the immune system and thereby improve the microenvironment, ultimately promoting endogenous repair.
Previous MSC-based clinical trials have revealed that intravenously administered MSCs move to and
accumulate in the lungs. It is therefore believed that these stem cells, when trapped in the lungs, could improve the pulmonary environment by alleviating inflammation and counteracting the cytokine storm, thereby protecting alveolar cells, preventing pulmonary fibrosis and improving lung function. We will pay close attention to the results of these clinical trials, and be sure to share any positive findings.
Leng, Z., et al. Transplantation of AEC2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging and Disease. (April 2020) 11(2): 216-228.
Golchin, A., Seyedjafari, E. & Ardeshirylajimi, A. Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev and Rep (2020). https://doi.org/10.1007/s12015-020-09973-w
Atluri,S. Manchikanti,L. Hirsch,J.A. Expanded Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) as a Therapeutic Strategy In Managing Critically Ill COVID-19 Patients: The Case for Compassionate Use. Pain Physician (2020). 23:E71-E83