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.

Mechanisms of interactions between lung‐origin telocytes and mesenchymal stem cells to treat experimental acute lung injury

“…Conditioned medium from MSCs alone could restore sodium transport and preserve epithelial permeability probably through the regulation of growth factors. 24 Our data indicates that the mixture or co-appearance of some elements from MSCs and TCs may be necessary in restoration of endothelial barrier permeability.…”

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

“…Therefore, in recent years there has been a growing interest in exploring the effects of EVs specifically derived from MSCs in ARDS treatment. The biological rationale for the therapeutic use of these cell-free agents is comparable to stem cells including immune modulation and anti-inflammatory effects, promoting alveolar epithelium and endothelium repair, alveolar fluid clearance improvement, antimicrobial effects and inhibition of lung fibrosis [ 90 , 91 ]. Preclinical studies investigating EVs in ARDS as a therapeutic approach are in their infancy yet but several encouraging reports indicate that EVs derived from stem cells confer similar beneficial effects when compared to administration of stem cells themselves [ 90 – 92 ].…”

Utilizing Adipose Tissue-Derived Stem Cell Strategies for Obtaining Regeneration of Respiratory Tract Fistulas-A Systematic Review

“…Furthermore delivery of Adipose Stem Cells derived extracellular vesicles generated by mixing in a MSC mixed Thermoresponsive gel has been demonstrated to facilitate esophageal fistula healing in a thermoattenuated delivery strategy in a porcine model [102]. On this basis the delivery of Mesenchymal Stem/stromal Cells-derived secretome and vesicles has been posited to be a therapeutic approach in a lung injury and acute as well as chronic disease [103]. Significantly micro fragmented human adipose tissue has been demonstrated to enhance the paracrine anti-inflammatory, anti-fibrotic as well as proangiogenic properties that aids in corroborating tissue regeneration as compared to cultured MSC Cells [104].…”