Journal Article

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study

Shi, Meng-meng, Li, Ping, Dai, Cheng-xiang, Shen, Hong, Chen, De-chang, Wang, Jing, Zhu, Ying-Gang, Dong, Xuan, Qu, Jie-Ming, Xu, Cui-li, Monsel, Antoine, Li, Su-ke, Shen, Mei-ping, Chang, Jing, Ren, Cheng-jie

2022

Overview

Background Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 10 8 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 10 9 /L vs. 1.78 × 10 9 /L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 10 9 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration : MEXCOVID, NCT04276987.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adipose Tissue / Adipose tissues / Adverse events / Aerosols / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Body fat / Cell Biology / Cell number / Clinical outcomes / Clinical trials / Computed tomography / Coronaviruses / COVID-19 / COVID-19 - therapy / Enrollments / Exosomes / Extracellular vesicles / Female / Hospitals / Humans / Inhalation / Interleukin 6 / Laboratories / Life Sciences / Lymphocytes / Male / Medical research / Medicine, Experimental / Mesenchymal Stem Cells / Mesenchymal stromal cell / Mesenchyme / Middle Aged / Palliative care / Patients / Pilot Projects / Pneumonia / Pulmonary lesions / Regenerative Medicine/Tissue Engineering / Safety / Severe acute respiratory syndrome coronavirus 2 / Statistical analysis / Stem cell therapy of COVID-19 and other respiratory diseases / Stem Cells / Stromal cells / Toxicity / Vesicles