The possibility of using stem cells to treat COVID19 at first impression seems perplexing. Sure stem cells have been used to treat everything from heart failure to erectile dysfunction, still with no FDA clearances for major diseases. So how could stem cells be useful for treating a viral infection?
Well, it's not for treating the virus itself, but for treating a complication of the virus, specifically lung damage. It is well known in the field of stem cells that when cells are administered intravenously they get stuck in the lungs[1]. At least a majority of stem cells get “parked” in the lungs due to the size of the cells and the small diameter of the lung blood vessels which facilitate oxygen exchange. Subsequently, the cells exit the lung and circulate in the body. The fact that stem cells, particularly mesenchymal stem cells, have this propensity towards the lung makes them idea of use in conditions associated with lung inflammation[2].
In COVID-19 the main cause of death is a type of lung failure called acute respiratory distress syndrome [3-6]. In this condition, viral infection of lung cells causes significant inflammation, which elicits a hyperimmune response that kills both virus and health lung cells, which causes death.
Previous studies[2, 7, 8] have shown that administration of mesenchymal stem cells can help animals and humans which have been afflicted with ARDS. Unfortunately, in some studies strong therapeutic effects have not been seen. This may be because the cells utilized may not have been optimized for treatment of the condition. For example, if the inflammation in the lung is too advanced, the stem cells may be manipulated by the inflammation so that instead of healing they fail to function. Thus, it is important to not use “any old stem cell” but to identify and utilize optimized stem cells.
The group at Stemedica has pioneered the used of hypoxia treated stem cells[3, 9-11]. This is an advancement from the previous types of stem cells that were utilized because the hypoxia conditioning enhances the therapeutic activities of stem cells by “putting them on alert”. Let me explain. Hypoxia is reduction in oxygen. Under normal circumstances, stem cells should not be activated…under normal circumstances, stem cells circulate around the body, and once they recognize inflammation or “danger” signals, then they get activated and start performing their therapeutic functions, which include: a) producing anti-inflammatory mediators; b) generating signals that stimulate healing; and c) actually differentiating into and taking over the function of injured lung cells.
One of the “danger” signals that stem cells are activated by is lack of oxygen. When you think about it, pretty much any tissue injury involves blood clotting. When blood clots there is lack of oxygen. The lack of oxygen turns on a molecular switch called hypoxia inducible factor (HIF), which turns on a homing signal, called stromal derived factor (SDF)-1. SDF-1 “tells” stem cells that they are needed in the injured tissue. When stem cells arrive to the injured tissue, they “sense” there is a lack of oxygen. This lack of oxygen, called “hypoxia” instructs the stem cells that there is something wrong and the stem cells begin producing high amounts of growth factors, anti-inflammatory mediators, and immune modulatory cytokines.
Stemedica has issued patents on using this hypoxia as part of their manufacturing process. Accordingly, there is theoretical and practical support that the hypoxia treated stem cells of Stemedica may have some superior advantages to other approaches.
In a press release that appeared on April 20, 2020, the company Stemedica reported that a COVID-19 patient was treated with their stem cells at the Providence Saint John's Health Center, Santa Monica, CA. The clinician-scientists, Dr. Santosh Kesari, who is Director of Translational Neurosciences and Neurotherapeutics at John Wayne Cancer Institute, Pacific Neuroscience Institute, and Providence Saint John’s Health Center,stated in the press release “I was consulted about compassionate use options for a patient with respiratory failure from COVID-19 infection. The patient was not a candidate for currently available clinical trials and had already received treatment with anti-IL-6, anti-retrovirals, hydroxychloroquine, and convalescent plasma,” said Dr. Kesari. “Our team was running out of options.”
The successful treatment and lack of immediate adverse events points to the potential of these cells to treat other patients with COVID-19. It is important to note that Stemedica has already demonstrated these cells have therapeutic activity in a variety of settings including cardiac[3, 9-11], and may help other COVID-19 related pathologies in addition to lung damage.
Written by Tom Ichim, PhD
Keywords: CureScience, COVID, Stem Cells
1. Fischer, U.M., et al., Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev, 2009. 18(5): p. 683-92.
2. Mohammadipoor, A., et al., Therapeutic potential of products derived from mesenchymal stem/stromal cells in pulmonary disease. Respir Res, 2018. 19(1): p. 218.
3. Cramer, S.C., et al., Efficacy of Home-Based Telerehabilitation vs In-Clinic Therapy for Adults After Stroke: A Randomized Clinical Trial. JAMA Neurol, 2019. 76(9): p. 1079-87.
4. McGonagle, D., et al., The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev, 2020: p. 102537.
5. Ramanathan, K., et al., Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Lancet Respir Med, 2020.
6. Tang, X., et al., Comparison of Hospitalized Patients With ARDS Caused by COVID-19 and H1N1. Chest, 2020.
7. Walter, J., L.B. Ware, and M.A. Matthay, Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis. Lancet Respir Med, 2014. 2(12): p. 1016-26.
8. Wilson, J.G., et al., Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med, 2015. 3(1): p. 24-32.
9. Butler, J., et al., Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial. Circ Res, 2017. 120(2): p. 332-340.
10. Harach, T., et al., Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease. Neurobiol Aging, 2017. 51: p. 83-96.
11. Levy, M.L., et al., Phase I/II Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke. Stroke, 2019. 50(10): p. 2835-2841.
Comments