Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases

ABSTRACT

Introduction: Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives.

Areas covered: The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases.

Expert opinion: While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.

KEYWORDS:

• Acute lung injury
• acute respiratory distress syndrome
• exosomes
• extracellular vesicles
• mesenchymal stem cells
• microvesicles

Article highlights

• MSC-derived CM recapitulated the therapeutic effects of MSC in ALI and other inflammatory lung diseases through activation of anti-inflammatory, pro-survival, and anti-apoptotic pathways.

• MSC-derived CM as a therapeutic has limitations due to the lack of standardization in terms of the preconditioning process as well as the optimal therapeutic dose, timing, and route of administration.

• By maintaining the therapeutic advantages of MSC without the inherent risk of iatrogenic tumor formation, MSC-derived EV represent an attractive area of research for treating inflammatory lung diseases, including ALI.

• The mechanisms underlying the therapeutic effect of MSC-derived EVs appears to derive from the transfer of its content which include mRNA, microRNA, proteins, receptors, and possibly organelles to the injured tissue.

• Utilization of MSC-derived EV will require large-scale production and standardization concerning identification, characterization, and quantification.

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Declaration of interest

This work was supported by the International Research Grant from the Société Française d’Anesthésie-Réanimation (Paris, France)(A.M.); by the Medical Research Grant from the group Pasteur-Mutualité (Paris, France) (A.M.); by the National Institutes of Health grant HL-113022 (J.W.L.). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.