The impact of the inflammatory pulmonary microenvironment on the behavior and function of mesenchymal stromal cells

Acute respiratory distress syndrome is characterized by the dysregulation and activation of several inflammatory pathways which lead to widespread inflammation in the lungs. Presently, direct therapy is unavailable and the use of mesenchymal stromal cells as a direct therapy has been proposed, as early-phase studies have shown promise.

MSCs exert various therapeutic effects on the inflammatory microenvironment, such as anti-microbial effects, restoration of the alveolar-capillary barrier, and exuding various anti-inflammatory effects. However, to exert these effects MSCs need to be submitted to specific external stimuli which can affect their immunomodulation, survival, migration and metabolic state. This review references several articles found through targeted searches in PubMed [Accessed between November 2024 and March 2025], for key terms such as 'mesenchymal stromal cells', 'inflammatory microenvironment', anti-inflammatory', 'metabolism', and 'immunomodulation'.

The advancement of MSCs therapy in the treatment of ARDS has not progressed as effectively as one might have anticipated. Several clinical findings have established patient subgroups based on inflammatory cytokine profiles and severity of ARDS. This variation in patients may influence the clinical efficacy of MSCs and instead of concluding that MSCs therapy is not worth pursuing, more research is needed to develop an appropriate therapy.