title: c-Kit immunoexpression delineates a putative endothelial progenitor cell population in developing human lungs.
abstract: Expression of c-Kit and its ligand, stem cell factor (SCF), in developing human lung tissue was investigated by immunohistochemistry. Twenty-eight human fetal lungs [age range 13 to 38 gestational wk (GW)] and 12 postnatal lungs (age range 1-79 yr) were evaluated. We identified c-Kit(+) cells in the lung mesenchyme as early as 13 GW. These mesenchymal c-Kit(+) cells in the lung did not express mast cell tryptase or α-smooth muscle actin. However, these cells did express CD34, VEGFR2, and Tie-2, indicating their endothelial lineage. Three-dimensional reconstructions of confocal laser scanning images revealed that c-Kit(+) cells displayed a closed-end tube formation that did not contain hematopoietic cells. From the pseudoglandular phase to the canalicular phase, c-Kit(+) cells appeared to continuously proliferate, to connect with central pulmonary vessels, and finally, to develop the lung capillary plexus. The spatial distribution of c-Kit- and SCF-positive cells was also demonstrated, and these cells were shown to be in close association. Our results suggest that c-Kit expression in early fetal lungs marks a progenitor population that is restricted to endothelial lineage. This study also suggests the potential involvement of c-Kit signaling in lung vascular development.
authors.affiliation: Dept. of Advanced Preventive Medicine for Infectious Disease, Tohoku Univ. School of Medicine, 2-1 Seiryoumachi, Aobaku, Sendai 980-8575, Japan. hkubo@med.tohoku.ac.jp.
authors.forename: Takaya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujino
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ota
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
mesh_terms: D000293:Adolescent; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: c-Kit; endothelial cells; lung development