Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment

Abstract

Background High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. Methods We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. Results No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). Conclusion Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. Trial registration: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947.

dCas9-Based PDGFR–β Activation ADSCs Accelerate Wound Healing in Diabetic Mice through Angiogenesis and ECM Remodeling

“…Genetically engineered cells do increase the efficacy of treatment, and gene–modified cell therapy appears to be safe and feasible at same time. In this study, we found that all ADSCs populations could continuously express PDGFR–β while the expression level decreased with passage, which maybe the cause of insufficient therapeutic potential reported in some clinical trials [ 31 , 32 , 33 ]. Moreover, if the PDGFR–β of MSCs used in these clinical trials were activated by the CRISPRa, it is possible that better therapeutic effects would be presented.…”

Effect and safety of mesenchymal stem cells for patients with COVID‐19: Systematic review and meta‐analysis with trial sequential analysis

“…52 Besides, MSCs can secrete anti-inflammatory cytokines such as interleukin (IL)-10, and IL-4, which could inhibit B cells and T cells, and NK cells activation. 32,56,57 And it has been proven that MSC therapy can alter macrophage polarity toward less inflammatory phenotypes by reducing the expression of CD83, CD11 and major compatibility complex II (MHC-II). 57 Last but not least, MSCs can contribute to improving profibrotic macrophage responses and lung F I G U R E 5 (A) Forrest plot of comparing the mesenchymal stem cells (MSCs) group and control group for the symptom remission rate of patients with coronavirus disease 2019 (COVID-19) using random-effect models with relative risk and 95% confidence intervals.…”

“…22,25,27,32 The inclusion criteria were different from each other, six studies included patients with critical COVID-19, 23,28,31,32,43,47 seven studies included severe patients, 22,24,25,29,30,42,46 only one study included not severe patients, 44 and the remaining studies had no limitations on the patient's severity of disease. 26,27,45 Except for 58.8% of studies used human umbilical cord-derived MSCs (hUC-MSCs), 22,23,25,26,[28][29][30]43,45,47 others use stem cell from menstrual blood, 24 peripheral blood, 27 placenta, 32 embryo, 44 and adipose. 42 In the eligible studies included in this analysis, the most common symptoms in MSCs-treated patients were fever, cough, and weakness.…”

“…The results showed that MSCs did not improve 30‐day mortality or 60‐day ventilator‐free days in COVID‐19 patients with moderate or severe ARDS, although it was safe 31 . Another study revealed that MSC therapy among COVID‐19 patients did not improve the mean LOS and serum oxygen saturation compared with standard treatment 32 …”

“…31 Another study revealed that MSC therapy among COVID-19 patients did not improve the mean LOS and serum oxygen saturation compared with standard treatment. 32 Because of the urgency of the epidemic, people around the world urgently want to know whether MSC-based treatment could benefit patients with COVID-19 and whether the treatment is safe.…”