The systemic administration of multipotent mesenchymal stromal cells alters the inflammatory response in the lung during murine polymicrobial sepsis

Sepsis is a life-threatening organ dysfunction and a major cause of acute respiratory distress syndrome (ARDS). Mesenchymal stromal cells (MSCs) have emerged as a potential immunomodulatory therapy, yet preclinical data remain inconsistent. This study investigated the early effects of human MSCs derived from different tissue sources-bone marrow (BMMSCs) and adipose tissue (ASCs)-on systemic and pulmonary inflammation in a murine model of polymicrobial sepsis. 60 male C57BL/6 mice underwent sham treatment, cecal ligation and puncture (CLP), or CLP followed by a single intravenous administration of BMMSCs or ASCs, manufactured according to GMP-compliant protocols. Analyses were performed 8, 24, and 72 h after CLP. Systemic inflammatory mediators were quantified by multiplex analysis, while pulmonary inflammation was assessed by mRNA and protein expression, histology, and immunofluorescence. CLP induced elevated systemic levels of pro-inflammatory mediators, which were not significantly reduced by MSC treatment. In lung tissue, however, MSC administration resulted in selective immunomodulatory effects. Expression of NLR family pyrin domain containing 3 (Nlrp3) was reduced in both MSC-treated groups, while ASC treatment additionally decreased pulmonary interleukin 6 (Il6) and complement 3a receptor (C3ar) mRNA expression at early time points. Protein levels of IL-1β, IL-6, and TNF-α were not significantly altered, although NLRP3 protein expression was reduced following ASC treatment. No significant differences in histological lung injury scores were observed between groups. In summary, MSC treatment induced modest, time-dependent attenuation of pulmonary inflammatory responses in polymicrobial sepsis without improving structural lung injury. No significant differences in pulmonary inflammatory gene expression, protein levels, or histological lung injury scores were observed between BMMSC- and ASC-treated groups, indicating that neither source demonstrated a clear immunomodulatory advantage over the other at the molecular endpoints assessed in this model.