Human placental mesenchymal stromal cell-derived small extracellular vesicles as a treatment for severe COVID-19: A double-blind randomized controlled clinical trial.

The current study aimed to investigate the effects of human placental mesenchymal stromal cell-derived small extracellular vesicles (hPMSC-sEVs) as a treatment for COVID-19. This double-blind, randomized, controlled clinical trial was conducted on two groups of patients with COVID-19-associated acute respiratory distress syndrome. After randomization, the control group received standard treatment and placebo, and the intervention arm received standard treatment plus hPMSC-sEVs. The number of hospital deaths was considered the primary outcome. After meeting the exclusion and inclusion criteria, 21 and 24 patients were allocated to intervention and control arms, respectively. Besides admission SpO2 levels, which were significantly lower in the intervention arm (p = 0.008), all the baseline demo-biographic and laboratory variables were similar between the groups. It was shown that hPMSC-sEVs could significantly (p = 0.015) decrease the mortality ratio in the intervention group (4/21 [19.04%]) compared to the controls (13/24 [54.16%]). The mean time to death in the intervention and control groups was 28.06 and 11.10 days, respectively (p < 0.001). This study showed that hPMSC-sEVs are a possible treatment for critically ill patients with COVID-19.

Improvement in the clinical manifestations of interstitial lung disease following treatment with placental mesenchymal stromal cell extracellular vesicles in a patient with systemic sclerosis: A case report.

Background: Interstitial lung disease (ILD) is a severe systemic sclerosis (SSc) complication with no current approved or golden standard treatment. This report aims to investigate the effectiveness of treatment with placental mesenchymal stromal cell (MSC) extracellular vesicles (EVs) in a patient with ILD due to SSc. Case presentation: The patient was a 55-year-old woman with a ten years history of SSc complicated by severe ILD. Over time, her lung disease progressed to interstitial fibrosis despite being treated with mycophenolate mofetil and monthly pulses of cyclophosphamide. Thus, she was treated with eight doses of placenta MSC-EVs. Four weeks after the third dose (Day 31 after the first dose), she reported marked improvement in her clinical symptoms, such as dyspnea and cough. Also, chest computed tomography (CT) scans demonstrated a significant reduction in ground glass consolidations and fibrotic changes. The patient was subsequently followed for twelve months, with findings showing significant improvement in exercise tolerance and reduced supplemental oxygen need. Conclusion: In this single case, placental MSC-EVs were seen to provide a potentially efficient treatment for SSc-related ILD; however, further investigation and clinical trials are necessary.