Stem/progenitor cells in lung development, injury repair, and regeneration.
Stem/progenitor cells in lung development, injury repair, and regeneration.
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DOI：
10.1513/pats.200801-012aw
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Driscoll, Barbara
中科院分区：
文献类型：
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作者：
Warburton, David;Perin, Laura;Driscoll, Barbara
至少两个上皮干/祖细胞群体产生肺原基，包括喉-气管复合体与第一支气管分叉下方的远端肺。远端群体的扩增需要FGF 9-FGF 10-FGFR 2b-Sprouty信号传导。成体干细胞的残余池被假设为肺再生和修复的来源。这些池位于上呼吸道的基底层内、肺神经内分泌细胞内或附近、支气管肺泡连接处以及肺泡上皮表面内。损伤后快速修复裸露的牙槽表面显然是生存的关键。增强内源性肺泡上皮修复的策略可以包括保护上皮祖细胞免受损伤和/或刺激内源性祖细胞功能。用肌苷或FGF信号传导的保护是可能的小分子治疗选择。或者，外源性干细胞/祖细胞可以通过静脉内、气管内或通过直接注射递送到肺中。目前在急性肺损伤修复的背景下正在评估的外源性干细胞/祖细胞的来源包括胚胎干细胞、骨髓或脂肪来源的间充质干细胞、循环内皮祖细胞以及最近的羊水干细胞/祖细胞。将干/祖细胞疗法转化为肺还需要进一步的工作。
At least two populations of epithelial stem/progenitor cells give rise to the lung anlage, comprising the laryngo-tracheal complex versus the distal lung below the first bronchial bifurcation. Amplification of the distal population requires FGF9-FGF10-FGFR2b-Sprouty signaling. Residual pools of adult stem cells are hypothesized to be the source of lung regeneration and repair. These pools have been located within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction as well as within the alveolar epithelial surface. Rapid repair of the denuded alveolar surface after injury is clearly key to survival. Strategies to enhance endogenous alveolar epithelial repair could include protection of epithelial progenitors from injury and/or stimulation of endogenous progenitor cell function. Protection with inosine or FGF signaling are possible small molecule therapeutic options. Alternatively, exogenous stem/progenitor cells can be delivered into the lung either intravenously, intratracheally, or by direct injection. Sources of exogenous stem/progenitor cells that are currently under evaluation in the context of acute lung injury repair include embryonic stem cells, bone marrow- or fat-derived mesenchymal stem cells, circulating endothelial progenitors, and, recently, amniotic fluid stem/progenitor cells. Further work will be needed to translate stem/progenitor cell therapy for the lung.