The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation.
The pathology of bleomycin-induced fibrosis is associated with loss of resident lung mesenchymal stem cells that regulate effector T-cell proliferation.
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DOI：
10.1002/stem.604
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发表时间：
2011-04
期刊：
影响因子：
5.2
通讯作者：
Majka, Susan M.
中科院分区：
文献类型：
--
作者：
Jun, Du;Garat, Chrystelle;West, James;Thorn, Nathalie;Chow, Kelsey;Cleaver, Timothy;Sullivan, Timothy;Torchia, Enrique C.;Childs, Christine;Shade, Theodore;Tadjali, Mehrdad;Lara, Abigail;Nozik-Grayck, Eva;Malkoski, Stephen;Sorrentino, Brian;Meyrick, Barbara;Klemm, Dwight;Rojas, Mauricio;Wagner, David H., Jr.;Majka, Susan M.
组织驻留间充质干细胞（MSC）是组织修复或再生、纤维化、炎症、血管生成和肿瘤形成的重要调节因子。在这里，我们定义了一组常驻肺间充质干细胞 (luMSC)，其功能是通过调节 T 细胞反应来调节博来霉素损伤的严重程度。博莱霉素诱导这些内源性 luMSC 的损失，并引发纤维化 (PF)、炎症和肺动脉高压 (PAH)。通过给予分离的 luMSC 来替代常驻干细胞，可以减轻博来霉素相关的病理并减轻 PAH 的发展。此外，luMSC 调节支气管肺泡液中淋巴细胞和粒细胞数量的减少，并在体外显示出对效应 T 细胞增殖的抑制作用。全局基因表达分析表明，luMSC 是一种独特的基质群体，在促炎介质和促纤维化途径方面不同于肺成纤维细胞。我们的结果表明，luMSC 具有保护损伤后肺完整性的功能，但是当内源性 MSC 丢失时，该功能就会受到损害，说明了这一新群体在肺损伤期间的重要性。在小鼠和人类肺组织中对这一群体的体内定义有助于制定旨在拯救内源性细胞以促进损伤期间肺修复的治疗策略。
Tissue resident mesenchymal stem cells (MSC) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Here we define a population of resident lung mesenchymal stem cells (luMSC) that function to regulate the severity of bleomycin injury via modulation of the T-cell response. Bleomycin induced loss of these endogenous luMSC and elicited fibrosis (PF), inflammation and pulmonary arterial hypertension (PAH). Replacement of resident stem cells by administration of isolated luMSC attenuated the bleomycin-associated pathology and mitigated the development of PAH. In addition, luMSC modulated a decrease in numbers of lymphocytes and granulocytes in bronchoalveolar fluid and demonstrated an inhibition of effector T cell proliferation in vitro. Global gene expression analysis indicated that the luMSC are a unique stromal population differing from lung fibroblasts in terms of proinflammatory mediators and pro-fibrotic pathways. Our results demonstrate that luMSCs function to protect lung integrity following injury however when endogenous MSC are lost this function is compromised illustrating the importance of this novel population during lung injury. The definition of this population in vivo in both murine and human pulmonary tissue facilitates the development of a therapeutic strategy directed at the rescue of endogenous cells to facilitate lung repair during injury.
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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：
20.3
作者：
Beltrami, Antonio R.;Cesselli, Daniela;Beltrami, Carlo A.
通讯作者：
Beltrami, Carlo A.
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
DOI：
10.1073/pnas.0704421104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Ortiz, Luis A.;DuTreil, Maria;Phinney, Donald G.
通讯作者：
Phinney, Donald G.