Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils.
Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils.
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DOI：
10.1002/stem.1270
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发表时间：
2013-02
期刊：
影响因子：
5.2
通讯作者：
Perrella, Mark A.
中科院分区：
文献类型：
--
作者：
Hall, Sean R. R.;Tsoyi, Konstantin;Ith, Bonna;Padera, Robert F., Jr.;Lederer, James A.;Wang, Zhihong;Liu, Xiaoli;Perrella, Mark A.
关键词：
使用间充质基质细胞（MSC）治疗细菌感染，包括全身性过程，如败血症，是一个不断发展的研究领域。本研究旨在探讨从密质骨中收获的MSC在盲肠结扎穿孔（CLP）诱导的多微生物脓毒症中的潜在用途及其与先天免疫系统的相互作用。我们还想阐明内源性HO-1在全身性细菌感染过程中在MSC中的作用。从血红素加氧酶（HO）-1缺陷（−/−）和野生型（+/+）小鼠的骨骼中收获的MSC在盲肠结扎和穿刺（CLP）诱导的多微生物脓毒症发作后给药时，与给药成纤维细胞对照细胞相比，改善了HO-1−/−和HO-1+/+受体小鼠的存活率。来源于小鼠密质骨的MSC增强了中性粒细胞在体外和体内吞噬细菌的能力，并促进CLP后腹膜和血液中的细菌清除。此外，在受体小鼠中耗尽中性粒细胞后，MSC的有益作用完全丧失，证明了中性粒细胞对于MSC应答的重要性。当在脓毒症发作后给药时，MSC还减少了易感HO-1−/−小鼠的多器官损伤。总之，这些数据表明，在多微生物脓毒症发作后用MSC治疗的有益效果不依赖于内源性HO-1表达，并且中性粒细胞对于这种治疗反应至关重要。
The use of mesenchymal stromal cells (MSCs) for treatment of bacterial infections, including systemic processes like sepsis, is an evolving field of investigation. The present study was designed to investigate the potential use of MSCs, harvested from compact bone, and their interactions with the innate immune system, during polymicrobial sepsis induced by cecal ligation and puncture (CLP). We also wanted to elucidate the role of endogenous HO-1 in MSCs during a systemic bacterial infection. MSCs harvested from the bones of heme oxygenase (HO)-1 deficient (−/−) and wild-type (+/+) mice improved the survival of HO-1−/− and HO-1+/+ recipient mice when administered after the onset of polymicrobial sepsis induced by cecal ligation and puncture (CLP), compared with the administration of fibroblast control cells. The MSCs, originating from compact bone in mice, enhanced the ability of neutrophils to phagocytize bacteria in vitro and in vivo, and to promote bacterial clearance in the peritoneum and blood after CLP. Moreover, after depleting neutrophils in recipient mice, the beneficial effects of MSCs were entirely lost, demonstrating the importance of neutrophils for this MSC response. MSCs also decreased multiple organ injury in susceptible HO-1−/− mice, when administered after the onset of sepsis. Taken together, these data demonstrate that the beneficial effects of treatment with MSCs after the onset of polymicrobial sepsis is not dependent on endogenous HO-1 expression, and that neutrophils are crucial for this therapeutic response.
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DOI：
10.1164/rccm.200902-0242oc
发表时间：
2009-12-01
影响因子：
24.7
作者：
Aslam, Muhammad;Baveja, Rajiv;Kourembanas, Stella
通讯作者：
Kourembanas, Stella
影响因子：
3.7
作者：
Gille, C;Spring, B;Orlikowsky, T
通讯作者：
Orlikowsky, T
影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
影响因子：
4.6
作者：
Lee JW;Gupta N;Serikov V;Matthay MA
通讯作者：
Matthay MA
影响因子：
15.9
作者：
Chung, Su Wol;Liu, Xiaoli;Perrella, Mark A.
通讯作者：
Perrella, Mark A.