Characterization of stem cells in human airway capable of reconstituting a fully differentiated bronchial epithelium

Characterization of stem cells in human airway capable of reconstituting a fully differentiated bronchial epithelium
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人类气道中能够重建完全分化的支气管上皮的干细胞的表征

DOI:
10.1007/bf02255823
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发表时间:
1995
期刊:
Somatic Cell and Molecular Genetics
影响因子:
--
通讯作者:
James M. Wilson
James M. Wilson
中科院分区:
--
文献类型:
--
作者:
M. Zepeda;M. R. Chinoy;James M. Wilson

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肺上皮是复杂的结构,在正常肺生理中起重要作用,并经常参与肺部疾病的病理生理。这些上皮内的细胞更新、谱系和分化的动力学是复杂的,而且人们对其知之甚少。我们将逆转录病毒介导的基因转移技术与人类近端气道异种移植模型相结合,以评估人类支气管上皮细胞增殖和分化的途径。用表达不同报告基因的重组逆转录病毒混合物感染人支气管上皮细胞(HBECs)原代分离物,将其接种于脱毛大鼠气管内,并皮下植入胸腺小鼠。让HBECs在异种移植物中再生四周,然后将其移植。在再生的人支气管上皮细胞中检测到单个逆转录病毒标记细胞的克隆扩增为表达转基因的细胞簇。无性系大小随播种密度的变化而变化,最大无性系包含103-104个细胞。相当数量的克隆在基底和分化柱状细胞中显示转基因表达,这一发现似乎与克隆大小无关。这些研究证明了人支气管上皮内存在一种能够广泛自我更新和多能性发育的细胞类型。进一步表征这些潜在的干细胞将对确定肺部疾病的发病机制和开发新的治疗方法(如基因治疗)至关重要。
The epithelia of the lung are complex structures that play an important role in normal lung physiology and are often involved in the pathophysiology of pulmonary diseases. The dynamics of cell turnover, lineage, and differentiation within these epithelia are complex and poorly understood. We have coupled the technique of retrovirus-mediated gene transfer with a xenograft model of proximal human airway to evaluate pathways of cellular proliferation and differentiation in human bronchial epithelia. Primary isolates of human bronchial epithelial cells (HBECs) were infected with mixtures of recombinant retroviruses expressing different reporter genes and seeded into denuded rat trachea, which were implanted subcutaneously into athymic mice. The HBECs were allowed to regenerate for four weeks in xenografts, which were then explanted. Clonal expansion of individual retrovirus-marked cells in the regenerated human bronchial epithelium was detected as clusters of transgene-expressing cells. Clone size varied with seeding density, resulting in the largest clones comprising 103–104 cells. A substantial number of clones showed transgene expression in basal as well as differentiated columnar cells, a finding that appeared independent of clone size. These studies demonstrate the existence of a cell type within the human bronchial epithelium that is capable of extensive self-renewal and pluripotent development. Further characterization of these potential stem cells will be important in defining pathogenesis of pulmonary diseases and in developing novel approaches to treatment such as gene therapy.
原代细胞培养物中气管粘液纤毛上皮的分化概括了仓鼠受伤后的正常胎儿发育和再生。
DOI: --
发表时间: 1987
期刊: The American journal of pathology
影响因子: --
作者:
McDowell,EM;Ben,T;Newkirk,C;Chang,S;DeLuca,LM
通讯作者: DeLuca,LM
DOI: 10.1172/jci117028
发表时间: 1994-02-01
影响因子: 15.9
作者:
ENGELHARDT, JF;ZEPEDA, M;WILSON, JM
通讯作者: WILSON, JM