Interleukin-10-engineered mesenchymal stem/stromal cells exhibit robust immunomodulatory effects in vitro and in vivo

• IL-10-engineered MSCs (MSC-IL-10) maintain mesenchymal phenotype and multipotency while secreting robust IL-10, enhancing their immunomodulatory capacity. • MSC-IL-10 significantly reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12) and Nos2 expression in vitro, outperforming wild-type MSCs. • In LPS-induced endotoxemia, MSC-IL-10 treatment lowers systemic inflammation, restores leukocyte counts, and attenuates CD11b⁺ inflammatory cell recruitment, surpassing MSC-WT. • MSC-IL-10 mitigates lung tissue damage and biodistributes to liver, lungs, and spleen, supporting its potential as a cell-based therapy for sepsis and inflammatory disorders.