The extrapulmonary origin of fibroblasts: stem/progenitor cells and beyond.
The extrapulmonary origin of fibroblasts: stem/progenitor cells and beyond.
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DOI：
10.1513/pats.200512-133tk
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Phan, Sem H
中科院分区：
文献类型：
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作者：
Lama, Vibha N;Phan, Sem H
尽管肺内祖细胞传统上被认为是响应于肺损伤的再生细胞的来源，但最近越来越多的证据表明，参与这种修复/重塑过程的间充质细胞的显著比例可能来源于肺外来源，例如最近描述的循环纤维细胞以及其他骨髓来源的祖细胞。追踪纤维细胞的CD 34和/或CD 45标记物的研究显示它们存在于受损的鼠肺组织中。此外，具有表达绿色荧光蛋白（GFP）的骨髓细胞的骨髓嵌合小鼠在肺损伤后的肺中显示出丰富的表达GFP的成纤维细胞。然而，尽管纤维细胞表达CD 34和CD 45，并且似乎具有分化为肌成纤维细胞的能力，但这些特性在骨髓来源的成纤维细胞中并不明显。在损伤的肺组织中诱导CCL 21（SLC）和CXCR 12（SDF 1 α），以及在来自损伤的肺的成纤维细胞中诱导它们各自的同源受体CCR 7和CXCR 4，表明通过这些趋化因子募集这些肺外祖细胞。这得到CXCR 12的抗体中和减少纤维细胞募集和肺纤维化的证据的支持。相反，其他研究表明对骨髓来源的细胞具有保护作用。因此，虽然表明肺外成纤维细胞祖细胞的流入是对肺损伤的反应，但这些最近的研究还没有提供关于募集细胞的实际表型和命运、骨髓中祖细胞群体的身份以及最重要的是这些细胞在特发性间质性肺炎发病机制中的功能或作用的明确见解。
Although intrapulmonary progenitor cells are traditionally believed to be the source for regenerating cells in response to lung injury, recent mounting evidence indicates that a significant proportion of the mesenchymal cells involved in this repair/remodeling process may be derived from extrapulmonary sources, such as the recently described circulating fibrocyte as well as other bone marrow-derived progenitor cells. Studies tracking CD34 and/or CD45 markers of fibrocytes show their presence in injured murine lung tissue. Moreover, bone marrow chimeric mice with green fluorescence protein (GFP)-expressing marrow cells show abundant GFP-expressing fibroblasts in their lungs in response to lung injury. However, although fibrocytes express CD34 and CD45, and appear to have the capacity to differentiate to myofibroblasts, these properties are not evident in the bone marrow-derived fibroblasts. Induction of CCL21 (SLC) and CXCR12 (SDF1alpha) in injured lung tissue, and their respective cognate receptors, CCR7 and CXCR4, in fibroblasts from injured lungs, suggests recruitment of these extrapulmonary progenitor cells via these chemokines. This is supported by evidence that antibody neutralization of CXCR12 reduces recruitment of fibrocytes and pulmonary fibrosis. In contrast, other studies suggest a protective effect for bone marrow-derived cells. Thus, although suggesting that influx of extrapulmonary fibroblast progenitor cells occurs in response to lung injury, these recent studies do not yet provide clear insight as to the actual phenotype and fate of the recruited cells, the identity of the progenitor cell population in bone marrow, and most important, the function or role of these cells in pathogenesis of the idiopathic interstitial pneumonias.