Iman Seyhoun1, Neda Alijani2, Javad Verdi3, Mahshid Saleh4, Amir Abbas Vaezi5, Rasoul Aliannejad6,7, Amir Ali Sohrabpour8, Seyedeh Zahra Fotook Kiaei9, Mahdi Shadnoush10, Vahid Siavashi11, Leila Aghaghazvini12, Batoul Khoundabi13, Shahriyar Abdoli14, Bahram Chahardouli15. 1. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. i.seihoon@gmail.com. 2. Department of Infectious Diseases, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. n-alijani@sina.tums.ac.ir. 3. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. JavadVerdi2019@gmail.com. 4. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Internal Medicine, Alborz University of Medical Sciences, Karaj, Iran. 6. Department of Pulmonary and Critical Care, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 7. Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran. 8. Associate Professor of Gastroenterology and Hepatology, Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 9. Advanced Thoracic Research Centre, Tehran University of Medical Science, Tehran, Iran. 10. Department of Clinical Nutrition, Faculty of Nutrition & Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 11. Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. 12. Associate Professor, Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 13. Iran Helal Institute of Applied-Science and Technology, Research Center for Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, Iran. 14. Pasteur Institute of Iran, National Cell Bank of Iran, Tehran, Iran. 15. Hematology, Oncology, and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) have received particular attention because of their ability to modulate the immune system and inhibit inflammation caused by cytokine storms due to SARS-CoV-2. New alternative therapies may reduce mortality rates in patients with COVID19. This study aimed to assess the safety and efficacy of injecting intravenous Wharton's jelly-derived MSCs in patients with COVID-19 as a treatment. METHODS: In this study, five patients with severe COVID-19 were treated with Wharton's jelly-derived mesenchymal stem cells (150 × 106 cells per injection). These patients were subject to three intravenous injections 3 days apart, and monitoring was done on days 0, 3, 6, and 14 in routine tests, inflammatory cytokines, and flow cytometry of CD4 and CD8 markers. A lung CT scan was performed on base and days 14 and 28. In addition, IgM and IgG antibodies against SARS-CoV-2 were measured before and after treatment. RESULTS: The results showed that IL-10 and SDF-1 increased after cell therapy, but VEGF, TGF-β, IFN-γ, IL-6, and TNFα decreased. Routine hematology tests, myocardial enzyme tests, biochemical tests, and inflammation tests were performed for all patients before and after cell therapy on base and days 3, 6, and 14, which indicated the improvement of test results over time. COVID-19 antibody tests rose in 14 days after WJ-MSC injection. The total score of zonal involvement in both lungs was improved. CONCLUSIONS: In patients, the trend of tests was generally improving, and we experienced a reduction in inflammation. No serious complications were observed in patients except the headache in one of them, which was resolved without medication. In this study, we found that patients with severe COVID-19 in the inflammatory phase respond better to cell therapy. More extensive clinical trials should be performed in this regard. TRIAL REGISTRATION: IRCT, IRCT20190717044241N2 . Registered April 22, 2020.
BACKGROUND: Mesenchymal stem cells (MSCs) have received particular attention because of their ability to modulate the immune system and inhibit inflammation caused by cytokine storms due to SARS-CoV-2. New alternative therapies may reduce mortality rates in patients with COVID19. This study aimed to assess the safety and efficacy of injecting intravenous Wharton's jelly-derived MSCs in patients with COVID-19 as a treatment. METHODS: In this study, five patients with severe COVID-19 were treated with Wharton's jelly-derived mesenchymal stem cells (150 × 106 cells per injection). These patients were subject to three intravenous injections 3 days apart, and monitoring was done on days 0, 3, 6, and 14 in routine tests, inflammatory cytokines, and flow cytometry of CD4 and CD8 markers. A lung CT scan was performed on base and days 14 and 28. In addition, IgM and IgG antibodies against SARS-CoV-2 were measured before and after treatment. RESULTS: The results showed that IL-10 and SDF-1 increased after cell therapy, but VEGF, TGF-β, IFN-γ, IL-6, and TNFα decreased. Routine hematology tests, myocardial enzyme tests, biochemical tests, and inflammation tests were performed for all patients before and after cell therapy on base and days 3, 6, and 14, which indicated the improvement of test results over time. COVID-19 antibody tests rose in 14 days after WJ-MSC injection. The total score of zonal involvement in both lungs was improved. CONCLUSIONS: In patients, the trend of tests was generally improving, and we experienced a reduction in inflammation. No serious complications were observed in patients except the headache in one of them, which was resolved without medication. In this study, we found that patients with severe COVID-19 in the inflammatory phase respond better to cell therapy. More extensive clinical trials should be performed in this regard. TRIAL REGISTRATION: IRCT, IRCT20190717044241N2 . Registered April 22, 2020.
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