Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior

Ahmed E. Hegab, Daisuke Arai, Jingtao Gao, Aoi Kuroda, Hiroyuki Yasuda, Makoto Ishii, Katsuhiko Naoki, Kenzo Soejima, Tomoko Betsuyaku

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.

Original languageEnglish
Pages (from-to)109-121
Number of pages13
JournalStem Cell Research
Volume15
Issue number1
DOIs
Publication statusPublished - 2015 Jul 1

Fingerprint

Stem Cells
Epithelial Cells
Lung
Stem Cell Niche
Stromal Cells
Coculture Techniques
Endothelial Cells
Fibroblasts
Organoids
Stem Cell Factor
Fibroblast Growth Factor 2
Cellular Structures
Trachea
Homeostasis
In Vitro Techniques
Wounds and Injuries
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior. / Hegab, Ahmed E.; Arai, Daisuke; Gao, Jingtao; Kuroda, Aoi; Yasuda, Hiroyuki; Ishii, Makoto; Naoki, Katsuhiko; Soejima, Kenzo; Betsuyaku, Tomoko.

In: Stem Cell Research, Vol. 15, No. 1, 01.07.2015, p. 109-121.

Research output: Contribution to journalArticle

Hegab, Ahmed E. ; Arai, Daisuke ; Gao, Jingtao ; Kuroda, Aoi ; Yasuda, Hiroyuki ; Ishii, Makoto ; Naoki, Katsuhiko ; Soejima, Kenzo ; Betsuyaku, Tomoko. / Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior. In: Stem Cell Research. 2015 ; Vol. 15, No. 1. pp. 109-121.
@article{d9c9e01b795c4f909d5eb905160841e4,
title = "Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior",
abstract = "The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.",
author = "Hegab, {Ahmed E.} and Daisuke Arai and Jingtao Gao and Aoi Kuroda and Hiroyuki Yasuda and Makoto Ishii and Katsuhiko Naoki and Kenzo Soejima and Tomoko Betsuyaku",
year = "2015",
month = "7",
day = "1",
doi = "10.1016/j.scr.2015.05.005",
language = "English",
volume = "15",
pages = "109--121",
journal = "Stem Cell Research",
issn = "1873-5061",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior

AU - Hegab, Ahmed E.

AU - Arai, Daisuke

AU - Gao, Jingtao

AU - Kuroda, Aoi

AU - Yasuda, Hiroyuki

AU - Ishii, Makoto

AU - Naoki, Katsuhiko

AU - Soejima, Kenzo

AU - Betsuyaku, Tomoko

PY - 2015/7/1

Y1 - 2015/7/1

N2 - The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.

AB - The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.

UR - http://www.scopus.com/inward/record.url?scp=84930193758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930193758&partnerID=8YFLogxK

U2 - 10.1016/j.scr.2015.05.005

DO - 10.1016/j.scr.2015.05.005

M3 - Article

VL - 15

SP - 109

EP - 121

JO - Stem Cell Research

JF - Stem Cell Research

SN - 1873-5061

IS - 1

ER -