期刊
STEM CELL RESEARCH & THERAPY
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13287-021-02165-4
关键词
COVID-19; SARS-CoV-2; Pneumonia; Acute respiratory distress syndrome; Mesenchymal stromal cells; Cell therapy; Placenta; Umbilical cord
资金
- Tehran University of Medical Sciences [47136-97-1-99]
- Iranian Vice-President for Science and Technology, Barkat Pharmaceutical Group Pharmed
- Royesh Venture Capital Fund
This study investigated the safety and effectiveness of multiple high-dose infusions of MSCs derived from placenta and umbilical cord in critically ill COVID-19-induced ARDS patients. Some patients showed significant improvement in respiratory distress and reduction in inflammatory markers after cell infusions.
BackgroundAcute 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.MethodsA 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 (200x10(6) cells) every other day for a total of 600x10(6) human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases).FindingsThere were eight men and three women who were 42 to 66years 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 24-48h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7days (average: 4days), 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-alpha; 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-) levels decreased in four (P=0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19days (average: 10days) 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.InterpretationWe 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.
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