Therapeutic effects of mesenchymal stromal cell secretome in liver fibrosis with acute lung injury.

Chronic liver disease (CLD) is a widespread condition and liver fibrosis is a common hallmark. The COVID-19 pandemic has drawn awareness over emerging pathogens that pose severe risks for chronic disease patients, whose management is complicated because most drugs can overload liver metabolism, therefore therapeutic alternatives are needed. Aims: based on the difficulty of treating CLD patients during respiratory infections, this study focused on the therapeutic evaluation of adipose-derived mesenchymal stromal cell (ASC) secretome. Methods: the effects of ASC secretome were evaluated in a preclinical murine model of liver fibrosis induced by thioacetamide (TAA) and acute lung injury induced by lipopolysaccharide, using histological and cytokine profile analyses. ASC secretome exhibited therapeutic effects alleviating fibrogenesis and inflammation, decreasing plasmatic inflammatory markers (cytokines IL-6, IL-17A and TNF-α), and restoring immune homeostasis. The secretome reduced liver collagen accumulation and IL-6 levels and restored lung cytoarchitecture, decreasing levels of CD68 and TNF-α. These results provide a preclinical basis for potential clinical use of the ASC secretome and its products, advancing the concept of cell-free, systemically active interventions for complex tissue injuries, and reinforcing the potential of its paracrine factors to modify pathological responses and promote tissue regeneration in combined chronic-acute diseases.