Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock.
Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock.
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DOI：
10.1371/journal.pone.0025171
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Holcomb JB
中科院分区：
文献类型：
--
作者：
Pati S;Gerber MH;Menge TD;Wataha KA;Zhao Y;Baumgartner JA;Zhao J;Letourneau PA;Huby MP;Baer LA;Salsbury JR;Kozar RA;Wade CE;Walker PA;Dash PK;Cox CS Jr;Doursout MF;Holcomb JB
出血性休克（HS）和创伤是目前全球年轻人死亡的主要原因。HS和创伤后的发病率和死亡率通常是多器官衰竭的结果，如急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS），这些疾病的治疗选择很少。骨髓间充质干细胞（MSCs）是一种多能干细胞群，在许多疾病的临床前和临床模型中显示出治疗前景。在本文中，肺内皮细胞（佩奇）的体外研究表明，来自MSC和MSC-PEC共培养物的条件培养基（CM）通过保留粘附连接（VE-钙粘蛋白和β-连环蛋白）来抑制PEC的通透性。在用来自MSC-PEC共培养物的CM处理的佩奇中，白细胞粘附和粘附分子表达（VCAM-1和ICAM-1）受到抑制。在我们对大鼠HS的体内研究中证实了MSC对肺内皮功能和炎症的调节作用的进一步支持。在轻度HS的大鼠“固定体积”模型中，我们表明IV施用的MSC有效地抑制治疗动物血清中炎性细胞因子和趋化因子的全身水平。在体内，MSC还抑制肺内皮通透性和肺水肿，同时保存血管内皮屏障蛋白：VE-钙粘蛋白，Claudin-1和Occludin-1。用MSC处理的肺中的白细胞浸润（CD 68和MPO阳性细胞）也减少。总之，这些数据表明，MSC，直接和通过可溶性因子，是血管内皮和炎症的有效稳定剂。这些数据是第一个证明骨髓间充质干细胞在HS中的治疗潜力，并对骨髓间充质干细胞作为HS诱导的肺损伤的细胞治疗的潜在用途具有影响。
Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and β-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC co-cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat “fixed volume” model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
17.1
作者：
London NR;Zhu W;Bozza FA;Smith MC;Greif DM;Sorensen LK;Chen L;Kaminoh Y;Chan AC;Passi SF;Day CW;Barnard DL;Zimmerman GA;Krasnow MA;Li DY
通讯作者：
Li DY
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：
7.5
作者：
Lampugnani, Maria Grazia;Dejanaa, Etisabetta
通讯作者：
Dejanaa, Etisabetta
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF