Amanda Edinger

Introduction: Acute respiratory distress syndrome (ARDS) is a lung condition characterized by bilateral lung infiltrates that results in hypoxia. ARDS can be secondary to a variety of disease processes or direct lung damage, however, the disease is characterized by diffuse alveolar damage leading to inefficient oxygen exchange between at the alveolar-capillary interface. Throughout the literature, it is clear that the mortality rate for ARDS remains high (40%)4  despite the current standard of care. Mesenchymal stem cells (MSCs) have shown to be a promising new therapy to potentially reduce alveolar damage in ARDS. This review aims to outline the current mechanisms by which MSC therapy can ameliorate the pathogenesis of ARDS. Methods: The primary research studies used in this review implemented a variety of experimental procedures. Flow cytometry was used to determine the cell population of lung fluid.2 Immunofluorescent imaging was utilized to visualize mitochondrial transfer4, and ELISA was used to measure levels of paracrine mediators in lung fluid.5 Results: Throughout the literature, several studies have demonstrated that MSCs may be an effective new therapy for ARDS. The mechanisms behind the effectiveness of MSC therapy are numerous and can be generally categorized as modulation the immune system or direct repair of the lung epithelium. Immune modulating mechanisms include release of paracrine factors that enhance anti-inflammatory processes and inhibit pro-inflammatory processes.2,3,4  Direct lung repair mechanisms help maintain lung epithelial cell junctions and reduce apoptosis of lung endothelial cells.5  Several pre-clinical studies demonstrate that the effects of MSCs occur through paracrine mechanisms, however, in a mouse model it was shown that MSCs enhance alveolar macrophage phagocytosis via transfer of MSC mitochondria through tunneling nanotube formation.4  Conclusions: The current literature suggests a promising future for the treatment of ARDS with MSCs. In pre-clinical rat models, the data show that MSCs effectively reduce inflammation and decrease lung injury scores through paracrine factors and mitochondrial transfer. The efficacy of MSCs as a therapy for ARDS has shown great promise in several pre-clinical studies, however, further research is needed elucidate the effectiveness of MSCs in human populations.

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2. Gore AV, Bible LE, Song K, Ligingston DH, Mohr Mesenchymal stem cells increase T-regulatory cells and improve healing following trauma and hemorrhagic shock. J Trauma Acute Care Surgery. 2015;79(1):48-52.
3. Zhu H, Xiong Y, Xia Y, et Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Acute Lung Injury Mice. Scientific Reports. 2017;7:39889.
4. Jackson MV, Morrison TJ, Doherty DF, et Mitochondrial Transfer via Tunneling Nanotubes is an Important Mechanism by Which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the In Vitro and In Vivo Models of ARDS. Stem Cells (Dayton, Ohio). 2016;34(8):2210-2223.
5. Yang Y, Hu S, Xu X, et The Vascular Endothelial Growth Factors-Expressing Character of Mesenchymal Stem Cells Plays a Positive Role in Treatment of Acute Lung Injury In Vivo. Mediators of Inflammation. 2016;2016:2347938.