Dose-specific efficacy of adipose-derived mesenchymal stem cells in septic mice

作者：Kui Li, Tao Wang, Rui Li, Fulai Xue, Guodan Zeng, Jingyao Zhang, Yuan Ma, Feng Li, Y. James Kang · 发表于：Stem Cell Research & Therapy · 年份：2023 · DOI：10.1186/s13287-023-03253-3 · 被引用次数：12 · 研究领域：Mesenchymal stem cell research、Tissue Engineering and Regenerative Medicine、Immune cells in cancer

Abstract Background Mesenchymal stem cells (MSCs) therapy for sepsis has been extensively studied in the past decade; however, the treatment regimen and mechanism of action of MSCs remain elusive. Here, we attempted to understand the efficacy and mechanism of action of MSCs on rescuing mice with sepsis. Methods A mouse model of sepsis was produced by cecal ligation and puncture (CLP). Allogeneic adipose-derived MSCs (ADSCs) were administered by intravenous infusion at 6 h after CLP, and dose-related effects of ADSCs on these mice were determined by survival rate, histopathological changes, biochemical and coagulation parameters, bacterial load, and plasma levels of endotoxin and inflammatory cytokines. The tissue distribution of intravenously infused ADSCs in septic mice was investigated by pre-labeling ADSCs with the lipophilic membrane dye PKH26. RNA sequencing analysis was performed to assess the transcriptional changes in peripheral blood mononuclear cells (PBMCs) and the liver. Results A significant therapeutic effect of ADSCs at a dose of 2 × 10 7 cells/kg in septic mice was evidenced by a remarkable reduction in mortality (35.89% vs. 8.89% survival rate), blood bacterial burden, systemic inflammation, and multiple organ damage. In contrast, ADSCs at a lower dose (1 × 10 7 cells/kg) failed to achieve any beneficial outcomes, while ADSCs at a higher dose (4 × 10 7 cells/kg) caused more early death within 24 h after CLP, retaining a steady survival rate of 21.42% thereaft...