Abstract

Introduction: Acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in patients with COVID-19. Despite numerous studies, therapies for ARDS in COVID-19 remain significantly limited. Currently, there have been reports of the efficient use of mesenchymal stem cell (MSC) for the treatment of ARDS. Several studies have reported that MSC produces anti-inflammatory cytokines, promotes the maturation of dendritic cells, and modulates NK cells. The safety of MSC therapy has been demonstrated in early-stage clinical studies with a relatively small number of patients. We investigated the influence of freeze-dried human placental mesenchymal stem cells (HPMSC) in a preclinical rodent model of ARDS. Methods: Sixty rats were randomly divided into three groups of 20: the first group was the control, the second group received dexamethasone, and the third group received HPMSC. Results: Survival was highest in the HPMSC group (75%, 95%CI: 50, 88) when compared to the control group. In a cox regression model, mortality of HPMSC group (HR: 11.30 [95% CI: 4.05, 31.50]) when compared to control was statistically significant (p < 0.001). Mortality in the dexamethasone (HR: 64.25 [95% CI: 32.71, 126.19]) was not statistically significant (p = 0.199). Plasma serum TNF-α levels were statistically significant in the HMPSC group when compared to the control (p < 0.001) and dexamethasone group (p < 0.001). Single factor ANOVA comparing TNF-α levels between all groups was also significant (p < 0.0001). Trends (Table 1) indicated that plasma serum cytokine levels for TNF-α, IL-1β, and Il-6 were less in the HPMSC group than the control and dexamethasone groups. Conclusions: These experiments demonstrated that HPMSC significantly decreased mortality, endogenous intoxication, and a reduction in the release of pro-inflammatory cytokines. The freeze-dried placental stem cell is a promising biomaterial that can be used nebulized for the treatment of coronavirus disease.

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