Cell therapy in patients with COVID-19 using Wharton’s jelly mesenchymal stem cells: a phase 1 clinical trial

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.

Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial

“…5 Many previous studies have shown that administration of mesenchymal stem cells is beneficial in reducing levels of inflammatory markers, such as IL-6 and ferritin. 20,21 Analysis of IL-10 levels in our study showed that the median value of IL-10 on the seventh day after the intervention in the intervention group was lower than in the control group, but there was no significant difference between both groups. In addition, there was a decrease in IL-10 levels on the 14th day after the intervention compared to IL-10 levels before the intervention in the secretome and control groups, and there was no significant difference between both groups.…”

“…19,20 Saleh et al (2021) conducted a study on five severe COVID-19 patients who were treated by Wharton's jelly-derived mesenchymal stem cells, and the results were a decrease in IL-6 and VEGF levels and an increase in IL-10 levels after the intervention. 21 Another study conducted by Adas et al (2021) stated that there were a decrease in IL-6 and ferritin levels and an increase in VEGF levels on the seventh day after the intervention with Wharton's jelly-derived mesenchymal stem cells in critically ill COVID-19 patients. 22 Analysis of IL-6 levels in our study showed that the median value of IL-6 in the intervention group was lower than the control group, both on the seventh day and 14 th day after the intervention.…”

Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application

“…Phase I and II clinical studies have shown that MSCs transplantation is a safe and potentially effective method for the treatment of moderate to severe ARDS [63,64]. Besides, recent exploratory clinical studies showed that MSCs treatment was associated with improvements in mortality, dyspnea and chest imaging findings for severe and critically ill COVID-19 patients [65][66][67][68][69]. And phase I and II clinical trials have also shown that intravenous MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated [70,71].…”

Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

“…MSC treatment was found to be safe and well-tolerated by patients. Further studies need to be conducted using control and treatment groups with increased sample sizes in order to draw conclusions about the efficacy of the treatment [ 100 ].…”