Phenotypic Analysis of BrdU Label-Retaining Cells during the Maturation of Conducting Airway Epithelium in a Porcine Lung

Phenotypic Analysis of BrdU Label-Retaining Cells during the Maturation of Conducting Airway Epithelium in a Porcine Lung
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猪肺传导气道上皮成熟过程中 BrdU 标记保留细胞的表型分析

DOI:
10.1155/2019/7043890
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发表时间:
2019-01-01
影响因子:
4.3
通讯作者:
Liu, Xiaoming
Liu, Xiaoming
中科院分区:
医学3区
文献类型:
--
作者:
Jia, Yuanyuan;You, Xuehong;Liu, Xiaoming

文献摘要

被引文献

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干细胞/祖细胞最近被证明在不同器官或组织的成熟、损伤修复和再生中发挥关键作用。猪的大部分器官在生理、细胞组成和大小上与人类相似,因此引起了人们对生物医学研究模型和异种移植的越来越大的兴趣。因此,猪器官或组织中干细胞/祖细胞的特征可能为更好地了解人类干细胞的生物学和功能提供了一条新的途径。通过对猪肺成熟过程中溴脱氧尿嘧啶核苷(BrdU)标记保留细胞(LRC)的形态计量分析,研究了猪肺传导上皮中潜在的干/祖细胞。结果表明,猪肺传导气道内可见由基细胞、纤毛细胞、杯状细胞和柱状细胞组成的假复层粘液纤毛上皮。此外,大多数能够在体外增殖的原代上皮细胞表达角蛋白5,这些角蛋白5阳性细胞的亚群也表达CD117(c-Kit)或CD49f(整合素α6,ITGA6),提示它们可能是猪肺传导气道的潜在上皮干/祖细胞。对BrdU标记的新生仔猪进行的谱系追踪分析表明,在肺成熟的90天期间,传导气道中BrdU标记细胞的比例下降。BrdU标记的上皮细胞也表达角蛋白14、粘蛋白5AC或前表面活性蛋白C,免疫组织化学和免疫荧光染色显示角蛋白14阳性细胞是BrdU标记的最常见的上皮细胞类型。本研究为研究猪和人上皮干/祖细胞在呼吸道传导中的生物学和功能提供了有价值的信息。
Stem/progenitor cells have recently been demonstrated to play key roles in the maturation, injury repair, and regeneration of distinct organs or tissues. Porcine has spurred an increased interest in biomedical research models and xenotransplantation, owing to most of its organs share similarities in physiology, cellular composition and size to humans. Therefore, characterization of stem/progenitor cells in porcine organs or tissues may provide a novel avenue to better understand the biology and function of stem cells in humans. In the present study, potential stem/progenitor cells in conducting airway epithelium of a porcine lung were characterized by morphometric analysis of bromodeoxyuridine (BrdU) label-retaining cells (LRCs) during the maturation of the lung. The results showed a pseudostratified mucociliary epithelium comprised of basal, ciliated, goblet, and columnar cells in the conducting airway of a porcine lung. In addition, the majority of primary epithelial cells able to proliferate in vitro expressed keratin 5, a subpopulation of these keratin 5-positive cells, also expressed CD117 (c-Kit) or CD49f (integrin alpha 6, ITGA6), implying that they might be potential epithelial stem/progenitor cells in conducting airway of a porcine lung. Lineage tracing analysis with a BrdU-labeled neonatal piglet showed that the proportion of BrdU-labeled cells in conducting airways decreased over the 90-day period of lung maturation. The BrdU-labeled epithelial cells also expressed keratin 14, mucin 5AC, or prosurfactant protein C (ProSP-C); among them, the keratin 14-positive cells were the most frequent BrdU-labeled epithelial cell type as determined by immunohistochemical and immunofluorescence staining. This study may provide valuable information on the biology and function of epithelial stem/progenitor cells in conducting airway of pigs and humans.