Mesenchymal stromal cell-derived exosomes for acute respiratory distress syndrome treatment: A review of preclinical and clinical trials

INTRODUCTION. During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) was diagnosed in 15–33% of patients hospitalised for pulmonary diseases. Hospital mortality rates increased. The existing medicinal products lacked effectiveness. Thus unconventional treatment methods were needed, such as mesenchymal stromal cell (MSC) therapy. The risk of blood clotting in the lung vessels after MSC injection made exosomes from MSC secretome a therapy of choice. Exosomes cross the blood-brain barrier and have regenerative effect similar to that of MSC. The promising results of preclinical trials for exosome-based drugs have stimulated their clinical use. Analysing their safety and effectiveness will allow us to develop protocols for their production, storage, and transportation, as well as optimal dose regimens for cell-free therapy of ARDS and other pulmonary diseases.

AIM. This study aimed to analyse performed preclinical and clinical studies on safety  and efficacy of MSC-derived exosome drugs intended for cell-free ARDS therapy and other pulmonary diseases as an alternative to drug therapy.

DISCUSSION. Exosomes, the most important secretome element in various cells, carry out horizontal transfer of genetic information and bioactive molecules. Animal models show that exosomes obtained from MSC secretome have regenerative abilities similar to MSC and offer various advantages: small size excluding blood clotting in the pulmonary capillaries; ability to penetrate blood-brain barrier, non-teratogenicity, and exchange of epigenomic information in cell-cell interactions. Preclinical in vivo studies have shown that exosomes affect regeneration of damaged lung tissue in ARDS and other lung diseases. Clinical trials have confirmed safety and effectiveness of inhalation, intravenous or combined administration. Drug effectiveness can be increased by combining exosomes with MSC or enriching them with CD24 (key molecule of innate immunity). Due to regenerative, immunomodulatory properties of exosomes, their ability to reduce the level of cytokine storm and apoptosis, they are used to treat ARDS and other lung diseases. Exosome preparations reverse ARDS and other diseases due to their regenerative and immunomodulatory effect, and ability to reduce cytokine storm and apoptosis. Thus exosomes are recognised as a new effective cell-free therapy.

CONCLUSIONS. Therapeutic effect of exosome-based preparations was analysed in experimental, preclinical, and clinical trials; however, further trials are required to determine ARDS safety and optimal treatment regimens.

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