Therapeutic potential of mesenchymal stem/stromal cell-derived secretome and vesicles for lung injury and disease

Abstract

Introduction: The acute respiratory distress syndrome (ARDS) is a devastating clinical condition common in patients with respiratory failure. Based largely on numerous preclinical studies and recent Phase I/II clinical trials, administration of stem cells, specifically mesenchymal stem or stromal cells (MSC), as a therapeutic for acute lung injury (ALI) holds great promise. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that stem cell-derived conditioned medium (CM) and/or extracellular vesicles (EV) might constitute compelling alternatives.Areas covered: The current review focuses on the preclinical studies testing MSC CM and/or EV as treatment for ALI and other inflammatory lung diseases.Expert opinion: Clinical application of MSC or their secreted CM may be limited by the cost of growing enough cells, the logistic of MSC storage, and the lack of standardization of what constitutes MSC CM. However, the clinical application of MSC EV remains promising, primarily due to the ability of EV to maintain the functional phenotype of the parent cell as a therapeutic. However, utilization of MSC EV will also require large-scale production, the cost of which may be prohibitive unless the potency of the EV can be increased.

Keywords: Acute lung injury; acute respiratory distress syndrome; exosomes; extracellular vesicles; mesenchymal stem or stromal cells; microvesicles.

Figures

Figure.. Schematic of the Possible Mechanisms Underlying the Therapeutic Effects of Mesenchymal Stem or Strom Cell Extracellular Vesicles.

Both exosomes and microvesicles released from MSC have shown reparative properties in pre-clinical lung injury models in terms of immunomodulation, repair of the alveolar epithelium and endothelium, suppression of fibrosis as well as reparative properties specific to ALI/ARDS (restoration of the alveolar fluid clearance and antimicrobial activity). Although MSC EV is being tested in an early Phase I clinical trial for preterm neonates with BPD, some major limitations to clinical use are whether the production and potency of the MSC can be scaled up or increased significantly to generate enough EV to treat larger size individuals such as adults.