Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice
Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice
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DOI：
10.1152/ajplung.00431.2006
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发表时间：
2007-07-01
影响因子：
4.9
通讯作者：
Rojas, Mauricio
中科院分区：
文献类型：
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作者：
Xu, Jianguo;Woods, Charles R.;Rojas, Mauricio
骨髓间充质干细胞（BMDMSCs）似乎对于修复博来霉素引起的小鼠慢性肺损伤很重要。为了确定这些 BMDMSC 对急性炎症反应的影响，我们向 C57BL/6 小鼠腹腔注射 1 mg/kg 内毒素，然后静脉输注 5 x 10(5) BMDMSC、相同数量的肺成纤维细胞或等体积的生理盐水溶液。内毒素处理后 6、24、48 小时和 14 天采集的肺显示，BMDMSC 给药可预防内毒素引起的肺部炎症、损伤和水肿。虽然我们能够在内毒素后 1 天检测到肺部的供体细胞，但到 14 天时仍未检测到供体细胞。 BMDMSC 给药抑制了内毒素诱导的循环促炎细胞因子的增加，而不降低抗炎介质的循环水平。 BMDMSC 和来自内毒素血症动物的肺细胞的离体共培养证明了双边对话，其中肺细胞刺激干细胞的增殖和迁移并抑制肺细胞产生促炎细胞因子。我们得出的结论是，BMDMSC 可以减少内毒素诱导的全身和局部炎症反应。这些效应不需要干细胞的肺移植或分化，并且至少部分归因于肺产生干细胞化学引诱物以及干细胞和肺细胞之间的体液和物理相互作用。我们推测，BMDMSC 群体的动员可能是调节急性炎症反应的一般机制。
Bone marrow- derived mesenchymal stem cells ( BMDMSCs) appear to be important in repair of the chronic lung injury caused by bleomycin in mice. To determine effects of these BMDMSCs on an acute inflammatory response, we injected C57BL/ 6 mice intraperitoneally with 1 mg/ kg endotoxin followed either by intravenous infusion of 5 x 10(5) BMDMSCs, the same number of lung fibroblasts, or an equal volume of normal saline solution. Lungs harvested 6, 24, and 48 h and 14 days after endotoxin showed that BMDMSC administration prevented endotoxin-induced lung inflammation, injury, and edema. Although we were able to detect donor cells in the lungs at 1 day after endotoxin, by 14 days no donor cells were detected. BMDMSC administration suppressed the endotoxin-induced increase in circulating proinflammatory cytokines without decreasing circulating levels of anti-inflammatory mediators. Ex vivo cocultures of BMDMSC and lung cells from endotoxemic animals demonstrated a bilateral conversation in which lung cells stimulated proliferation and migration of stem cells and suppressed proinflammatory cytokine production by lung cells. We conclude that BMDMSCs decrease both the systemic and local inflammatory responses induced by endotoxin. These effects do not require either lung engraftment or differentiation of the stem cells and are due at least in part to the production of stem cell chemoattractants by the lungs and to humoral and physical interactions between stem cells and lung cells. We speculate that mobilization of this population of BMDMSCs may be a general mechanism for modulating an acute inflammatory response.