Prospective Isolation of Bronchiolar Stem Cells Based Upon Immunophenotypic and Autofluorescence Characteristics

被引:69
作者
Teisanu, Roxana M. [1 ,2 ,3 ]
Lagasse, Eric [4 ]
Whitesides, John F.
Stripp, Barry R. [1 ,2 ,3 ]
机构
[1] Duke Univ, Med Ctr, Div Pulmonary Allergy & Crit Care, Durham, NC USA
[2] Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC USA
[3] Univ Pittsburgh, Sch Med, Dept Environm & Occupat Hlth, Pittsburgh, PA USA
[4] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA
关键词
Bronchiolar stem cell; Bronchioalveolar stem cell; Clara; Progenitor; Fractionation; Epithelium; LUNG-CANCER; CLARA CELL; EXPRESSION; RENEWAL; DIFFERENTIATION; IDENTIFICATION; PROLIFERATION; BRONCHOSCOPY; POPULATION; EPITHELIUM;
D O I
10.1634/stemcells.2008-0838
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Bronchiolar stem cells have been functionally defined in vivo on the basis of their resistance to chemical (naphthalene) injury, their infrequent proliferation relative to other progenitor cell types, and their coexpression of the airway and alveolar secretory cell markers Clara cell secretory protein and pro-surfactant protein C, respectively. Cell surface markers that have previously been used for their prospective isolation included Sca-1 and CD34. Using transgenic animal models associated with stem cell expansion, ablation, and lineage tracing, we demonstrate that CD34(pos) cells do not belong to the airway epithelial lineage and that cell surface Sca-1 immunoreactivity does not distinguish between bronchiolar stem and facultative transit-amplifying (Clara) cell populations. Furthermore, we show that high autofluorescence (AF(high)) is a distinguishing characteristic of Clara cells allowing for the fractionation of AF(low) bronchiolar stem cells. On the basis of these data we show that the de. ning phenotype of the bronchiolar stem cell is CD45(neg) CD31(neg) CD34(neg) Sca-l(low) AF(low). This refinement in the definition of bronchiolar stem cells provides a critical tool by which to assess functional and molecular distinctions between bronchiolar stem cells and the more abundant pool of facultative transit-amplifying (Clara) cells. STEM CELLS 2009; 27: 612-622
引用
收藏
页码:612 / 622
页数:11
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