Tags

Type your tag names separated by a space and hit enter

Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series.
Stem Cell Res Ther. 2021 01 29; 12(1):91.SC

Abstract

BACKGROUND

Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients.

METHODS

A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases).

FINDINGS

There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24-48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery.

INTERPRETATION

We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.

Authors+Show Affiliations

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran. Pulmonary Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Hematology and Cell Therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Student Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran.Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran. Pulmonary Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Department of Diabetes, Obesity, and Metabolism, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.Hematology and Cell Therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran. Pulmonary Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran. Pulmonary Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.Non-Commuting Diseases Research Center (NCDRC), Fasa University of Medical Sciences, Fasa, Iran.Department of Radiology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Medical Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran. Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.Department of Obstetrics and Gynecology, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.Cell-based Therapies Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran. mvasei@tums.ac.ir.Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. baharvand@royaninstitute.org. Department of Cell and Developmental Biology, Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran. baharvand@royaninstitute.org.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33514427

Citation

Hashemian, Seyed-Mohammad Reza, et al. "Mesenchymal Stem Cells Derived From Perinatal Tissues for Treatment of Critically Ill COVID-19-induced ARDS Patients: a Case Series." Stem Cell Research & Therapy, vol. 12, no. 1, 2021, p. 91.
Hashemian SR, Aliannejad R, Zarrabi M, et al. Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem Cell Res Ther. 2021;12(1):91.
Hashemian, S. R., Aliannejad, R., Zarrabi, M., Soleimani, M., Vosough, M., Hosseini, S. E., Hossieni, H., Keshel, S. H., Naderpour, Z., Hajizadeh-Saffar, E., Shajareh, E., Jamaati, H., Soufi-Zomorrod, M., Khavandgar, N., Alemi, H., Karimi, A., Pak, N., Rouzbahani, N. H., Nouri, M., ... Baharvand, H. (2021). Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem Cell Research & Therapy, 12(1), 91. https://doi.org/10.1186/s13287-021-02165-4
Hashemian SR, et al. Mesenchymal Stem Cells Derived From Perinatal Tissues for Treatment of Critically Ill COVID-19-induced ARDS Patients: a Case Series. Stem Cell Res Ther. 2021 01 29;12(1):91. PubMed PMID: 33514427.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. AU - Hashemian,Seyed-Mohammad Reza, AU - Aliannejad,Rasoul, AU - Zarrabi,Morteza, AU - Soleimani,Masoud, AU - Vosough,Massoud, AU - Hosseini,Seyedeh-Esmat, AU - Hossieni,Hamed, AU - Keshel,Saeid Heidari, AU - Naderpour,Zeinab, AU - Hajizadeh-Saffar,Ensiyeh, AU - Shajareh,Elham, AU - Jamaati,Hamidreza, AU - Soufi-Zomorrod,Mina, AU - Khavandgar,Naghmeh, AU - Alemi,Hediyeh, AU - Karimi,Aliasghar, AU - Pak,Neda, AU - Rouzbahani,Negin Hossieni, AU - Nouri,Masoumeh, AU - Sorouri,Majid, AU - Kashani,Ladan, AU - Madani,Hoda, AU - Aghdami,Nasser, AU - Vasei,Mohammad, AU - Baharvand,Hossein, Y1 - 2021/01/29/ PY - 2020/09/12/received PY - 2021/01/12/accepted PY - 2021/1/30/entrez PY - 2021/1/31/pubmed PY - 2021/2/17/medline KW - Acute respiratory distress syndrome KW - COVID-19 KW - Cell therapy KW - Mesenchymal stromal cells KW - Placenta KW - Pneumonia KW - SARS-CoV-2 KW - Umbilical cord SP - 91 EP - 91 JF - Stem cell research & therapy JO - Stem Cell Res Ther VL - 12 IS - 1 N2 - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients. METHODS: A total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases). FINDINGS: There were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24-48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery. INTERPRETATION: We suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS. SN - 1757-6512 UR - https://www.unboundmedicine.com/medline/citation/33514427/Mesenchymal_stem_cells_derived_from_perinatal_tissues_for_treatment_of_critically_ill_COVID_19_induced_ARDS_patients:_a_case_series_ L2 - https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02165-4 DB - PRIME DP - Unbound Medicine ER -