1 Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center , Rotterdam, The Netherlands .
Stem Cells Dev. 2013 Nov 1;22(21):2825-35. doi: 10.1089/scd.2013.0193. Epub 2013 Aug 9.
Mesenchymal stem cells (MSCs) have potent immunosuppressive effects in vitro and are considered as a therapeutic option for autoimmune disease and organ transplantation. While MSCs show beneficial effects on immune disease progression and transplant survival in animal models, the immunomodulatory mechanisms involved are largely unknown. In the present study, we show that intravenously infused C57BL/6- green fluorescent protein (GFP) MSCs home to the lungs in C57BL/6 recipient mice and induce an inflammatory response. This response was characterized by increased mRNA expression of monocyte chemoattractant protein-1 (MCP1), IL1-β, and TNF-α and an increase in macrophages in lung tissue 2 h after MSC infusion. Simultaneously, serum levels of proinflammatory IL6, CXCL1, and MCP1 protein increased, demonstrating systemic immune activation after MSC infusion. In liver tissue, no C57BL/6-GFP MSCs were detected, but MCP1 and TNF-α mRNA levels peaked 4 h after MSC infusion. The expression of the anti-inflammatory cytokines TGF-β, IL4, and IL10 was only marginally affected. Nevertheless, 3 days after MSC infusion, animals developed a milder inflammatory response to lipopolysaccharides. Our results suggest that the in vivo immunomodulatory effects of MSCs originate from an inflammatory response that is induced by the infusion of MSCs, which is followed by a phase of reduced immune reactivity.
间充质干细胞（MSCs）在体外具有强大的免疫抑制作用，被认为是自身免疫性疾病和器官移植的治疗选择。虽然 MSCs 在动物模型中对免疫疾病进展和移植存活表现出有益的影响，但涉及的免疫调节机制在很大程度上尚不清楚。在本研究中，我们表明，静脉内输注的 C57BL/6-绿色荧光蛋白（GFP）MSCs 归巢到 C57BL/6 受体小鼠的肺部，并诱导炎症反应。这种反应的特征是单核细胞趋化蛋白-1（MCP1）、IL1-β 和 TNF-α 的 mRNA 表达增加，以及 MSC 输注后 2 小时肺组织中巨噬细胞增加。同时，血清中促炎细胞因子 IL6、CXCL1 和 MCP1 蛋白水平升高，表明 MSC 输注后全身免疫激活。在肝组织中，未检测到 C57BL/6-GFP MSCs，但 MSC 输注后 4 小时 MCP1 和 TNF-α 的 mRNA 水平达到峰值。抗炎细胞因子 TGF-β、IL4 和 IL10 的表达仅略有影响。然而，MSC 输注 3 天后，动物对脂多糖产生了较轻的炎症反应。我们的结果表明，MSCs 的体内免疫调节作用源自 MSC 输注诱导的炎症反应，随后是免疫反应性降低的阶段。
