Mesenchymal Stem Cell-Educated Macrophages Ameliorate LPS-Induced Systemic Response.
Mesenchymal Stem Cell-Educated Macrophages Ameliorate LPS-Induced Systemic Response.
复制标题
间充质干细胞培养的巨噬细胞改善 LPS 诱导的全身反应
DOI：
10.1155/2016/3735452
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发表时间：
2016
影响因子：
4.6
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Hu Y;Qin C;Zheng G;Lai D;Tao H;Zhang Y;Qiu G;Ge M;Huang L;Chen L;Cheng B;Shu Q;Xu J
骨髓间充质干细胞和脂肪来源的间充质干细胞（ASCs）都具有免疫调节作用。本研究的目的是确定经ASCs诱导的巨噬细胞是否能在小鼠模型中直接改善脂多糖（LPS）诱导的全身反应。将小鼠腹腔巨噬细胞与ASCs在Transwell系统中共培养2天以诱导巨噬细胞。将小鼠分为5组：对照组、LPS组、LPS + ASCs组、LPS +未处理巨噬细胞组以及LPS +诱导后巨噬细胞组。诱导后的巨噬细胞减轻了肺部炎症、体重减轻、肺水肿以及炎症细胞因子反应。在体外，当巨噬细胞用LPS或急性呼吸窘迫综合征（ARDS）患者的血清处理时，ASCs增加了M2型巨噬细胞的表达，且此过程不依赖于细胞间的直接接触。在我们之前的临床试验中，当巨噬细胞用接受ASCs或安慰剂治疗的ARDS患者的血清培养时，ASCs治疗前后M2型巨噬细胞水平无差异，这表明对治疗方案的反应欠佳。ASCs在体外还降低了LPS诱导的促炎细胞因子水平，这一作用可被白细胞介素 - 10（IL - 10）模拟，且可被IL - 10和IL - 10受体的抗体阻断，这支持了诱导后的巨噬细胞通过IL - 10依赖机制发挥其抗炎作用的观点。
Both bone marrow and adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory effects. The goal of this study was to determine whether ASCs-educated macrophages could directly ameliorate LPS-induced systemic response in a mouse model. Mouse peritoneal macrophages were cocultured with ASCs in a Transwell system for 2 days to educate macrophages. Mice were divided into 5 groups: control, LPS, LPS + ASCs, LPS + untreated macrophages, and LPS + educated macrophages. Educated macrophages decreased lung inflammation, weight loss, pulmonary edema, and inflammatory cytokine response. In vitro, ASCs increased expression of M2 macrophages independent of direct cell-to-cell contact when macrophages were treated with LPS or serum from patients with acute respiratory distress syndrome (ARDS). When macrophages were cultured with serum from ARDS patients who were treated with ASCs or placebo in our previous clinical trial, there was no difference in M2 macrophage levels before and after ASCs treatment indicating a suboptimal response to the treatment protocol. ASCs also reduced the levels of LPS-induced proinflammatory cytokines in vitro which were mimicked by IL-10 and blocked by antibodies for IL-10 and IL-10 receptor supporting the notion that educated macrophages exert their anti-inflammatory effects via IL-10-dependent mechanisms.