Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Shock. 2011 Sep;36(3):235-41. doi: 10.1097/SHK.0b013e318225f6ae.
Mesenchymal stem cells (MSCs) possess immunomodulatory properties and may curtail the inflammatory response that characterizes sepsis and other systemic inflammatory states. We aimed to determine whether intravenous infusion of MSCs is associated with reduced inflammation and improved myocardial function in a rat model of endotoxemia. Adult Sprague-Dawley rats were administered saline (vehicle) or LPS (5 mg/kg) via tail vein injection. Treatments, either vehicle or 2 × 10(6) MSCs, were infused 1 h later via tail vein. Animals were randomly assigned to the following groups: (a) vehicle + vehicle (control; n = 6), (b) LPS + vehicle (n = 6), or (c) LPS + MSCs (n = 6). Six hours after induction of endotoxemia, left ventricular ejection fraction (EF) and fractional shortening (FS) was assessed via parasternal short-axis M-mode echocardiography. Hearts and serum were collected for determination of cytokine levels via enzyme-linked immunosorbent assay. Animals injected with LPS + vehicle exhibited depressed cardiac function as indicated by a 26% and 37% reduction in EF and FS from baseline, respectively. Treatment with MSCs was associated with improved cardiac function compared with vehicle treatment as indicated by a reduction in EF and FS of only 10% and 17%, respectively (P < 0.05). Myocardial levels of TNF-α, IL-1β, and IL-6 were elevated in LPS-treated animals versus control. Similarly, serum levels of IL-1β, IL-6, and IL-10 were increased in LPS-treated animals. Treatment with MSCs, however, was associated with significant reductions in serum levels of IL-1β and IL-6 and in myocardial levels of TNF-α, IL-1β, and IL-6. In addition, treatment with MSCs was associated with a further increase in serum IL-10. Infusion of MSCs modulates the systemic inflammatory response and is associated with improved cardiac function during endotoxemia.
间充质干细胞（MSCs）具有免疫调节特性，可能会减轻内毒素血症和其他全身炎症状态的特征性炎症反应。我们旨在确定静脉输注间充质干细胞是否与内毒素血症大鼠模型中炎症减少和心肌功能改善相关。成年 Sprague-Dawley 大鼠通过尾静脉注射给予生理盐水（载体）或 LPS（5mg/kg）。1 小时后，通过尾静脉输注载体或 2×106MSCs 进行治疗。动物随机分为以下组：（a）载体+载体（对照；n=6），（b）LPS+载体（n=6）或（c）LPS+MSCs（n=6）。内毒素血症诱导 6 小时后，通过胸骨旁短轴 M 模式超声心动图评估左心室射血分数（EF）和缩短分数（FS）。收集心脏和血清，通过酶联免疫吸附试验测定细胞因子水平。与载体处理相比，用 MSCs 处理的动物表现出改善的心脏功能，EF 和 FS 分别降低了 26%和 37%（P<0.05）。与 LPS 处理的动物相比，用 MSCs 处理与心肌 TNF-α、IL-1β 和 IL-6 水平降低有关，而 LPS 处理的动物血清中 IL-1β、IL-6 和 IL-10 水平升高。然而，用 MSCs 处理与血清中 IL-1β 和 IL-6 水平以及心肌 TNF-α、IL-1β 和 IL-6 水平显著降低有关。此外，用 MSCs 处理还与血清中 IL-10 水平进一步增加有关。输注 MSCs 可调节全身炎症反应，并与内毒素血症期间心脏功能改善相关。
