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Breathing Easy With Mesenchymal Stem Cells: COVID-19

H7N9 infection is caused by the family of influenza A viruses (IAVs); with 6 seasonal epidemics so far in mainland China since 2016 showing its developing virulence. The symptoms of H7N9 infection are fever, cough, shortness of breath, and sputum that develop into severe pneumonia and moderate-to-severe acute respiratory distress syndrome or ARDS. Another disease that has created history is the coronavirus disease 2019 (COVID-19) by spreading across the world. This disease shares a similar profile with that of H7N9 infections in terms of ARDS, inflammation and damage in the lung treated by Mesenchymal Stem Cells. Both these conditions lack efficient treatment or vaccines yet. This calls for a revolution in the treatment of H7N9 and COVID-19 given their induction of ARDS-induced severe pneumonia.

Before going ahead, let us see a previous report in the promise of MSCs in lung injury. Scientists Curley and team (2012)showed that bone-marrow-derived MSCs could lower lung damage in rat models of acute lung injury (ALI). 2 doses of Mesenchymal Stem Cells MSCs (2×106 cells) were given to rats exposed to injurious ventilation. Systemic oxygenation, lung structure and lung compliance were restored by MSCs while the inflammation and associated injury were lowered. Additionally, the total water content in the lung was also lowered: all these beneficial effects were not seen in controls.

Wilson and team (2015) conducted the stem cells for ARDS Treatment (START) trial: a multi centre, open-label, dose-escalation, phase 1 clinical trial. I was shown that transplantation of allogeneic MSCs in nine patients with ARDS showed no pre-specified adverse events showing the safety of MSCs.

Research by a recent team led by Jiajia Chen reported a clinical study of using mesenchymal stem cell (MSC)-based therapy for treating ADRS. The open-label clinical trial involved 17 patients with H7N9-induced ARDS as an experimental group while 44 patients with H7N9-induced ARDS were included as a control group. 1 million per kilogram of body weight of MSCs (3-4 infusions based on the patient) derived from menstrual-blood (of a healthy donor) were administered.

The multiple intravenous infusion of MSC was tolerated in these patients and no toxicity or serious adverse events were reported in any of these patients.

The lung function showed significant improvement at each follow-up. The mortality of the experimental group was lower than that of the control group (The death was 17.6% in the experimental group and 54.5% in the control group). 4 patients who were part of the five-year follow-up period manifested no toxic effects. This opens up the window of using MSCs for treating ADRS due to H7N9.

Given the similarity in the complications: ARDS and lung failure in both H7N9 and the coronavirus disease 2019 (COVID-19), the use of MSC-based therapy can be explored using more studies.

References:

Jiajia Chen, Chenxia Hu, Lijun Chen et al. Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment, Engineering, 2020, ISSN 2095-8099. https://doi.org/10.1016/j.eng.2020.02.006.

Curley GF, Hayes M, Ansari B, Shaw G, Ryan A, Barry F, O’Brien T, O’Toole D, Laffey JG. Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax. 2012;67:496–501.

J.G. Wilson, K.D. Liu, H. Zhuo, L. Caballero, M. McMillan, X. Fang, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med, 3 (2015), pp. 24-32.

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