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 .

Keywords: Acute respiratory distress syndrome (ARDS); COVID-19; Cell therapy; Coronavirus; Placenta mesenchymal stem cells (PL-MSC).

Fig. 1

Clinical trial flow chart. Structure and patient enrollment in the trial

Fig. 2

A PL-MSCs’ morphology under the inverted microscope with phase contrast, B CD markers expression pattern (the dotted black lines are isotype controls and the orange lines are the CD markers, C Differentiation of PL-MSCs into osteocytes (Alizarin Red staining) and adipocytes (Oil Red O staining), D results of karyotyping

Fig. 3

The changes in the vital signs 24 h after PL-MSC transplantation and comparison to the control group. Body temperature (A), heart rate (B), systolic blood pressure (C), and O₂ saturation (E) were increased after PL-MSC transplantation but the diastolic blood pressure (D) was decreased compared to the control group. None of these differences were statistically significant

Fig. 4

Duration of hospitalization (A), mortality (B)

Fig. 5

Alteration of CD4+ and CD8+ cells in patients with COVID-19 on day − 1 (before) and + 1 (after) PL-MSC transfusion were statistically insignificant (P ≥ 0.05)