Effective embryoid body formation from induced pluripotent stem cells for regeneration of respiratory epithelium

Otsuki, Koji; Imaizumi, Mitsuyoshi; Nomoto, Yukio; Nomoto, Mika; Wada, Ikuo; Miyake, Masakazu; Omori, Koichi

doi:10.1002/lary.24201

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…Embryoid bodies (EBs) were formed from tdTomato-labeled iPSCs in suspension culture over a period of 5 days in Knockout DMEM supplemented with 10% Knockout Serum Replacement (KSR) (Gibco), as described previously (Figure 1). 16 Briefly, iPSCs per 1 EB were seeded at a density of 1000 cells/well in low-adhesion 96-well plates. The EBs were then transferred to gelatin-coated Transwell inserts in 12-well plates (0.4-μm pore, 12-mm diameter, polyester; 4 EBs per well; Corning Inc, Corning, New York, USA) and cultured in serum-free differentiation medium comprising Knockout DMEM supplemented with 10% KSR, 100 ng/mL activin A, and 100 ng/mL basic fibroblast factor.…”

Section: Methodsmentioning

confidence: 99%

Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Ikeda

Imaizumi

Yoshie

et al. 2017

Ann Otol Rhinol Laryngol

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Section: Methodsmentioning

confidence: 99%

Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Ikeda

Imaizumi

Yoshie

et al. 2017

Ann Otol Rhinol Laryngol

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“…AT-2 cells or lung progenitor cells have been derived from human or mouse iPSCs and embryonic stem cells (ESCs) in several studies either through embryoid body (EB) formation or by using differentiation medium. Furthermore, administration of these iPSC-derived cells to mouse models of LPS-induced lung injury, bleomycininduced lung injury, and hyperoxia-induced lung injury has been shown to reduce injury, promote repair, and improve lung function [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. Therefore, iPSC-derived cells are considered to have therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration

et al. 2020

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Background Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles. Methods BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated. Results Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Conclusions Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.

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“…Induced pluripotent stem cells (iPSCs), which are obtained by introducing Yamanaka factors into differentiated somatic cells, display self-renewal properties and pluripotency [27]. AT-2 cells or lung progenitor cells have been derived from mouse iPSCs or embryonic stem cells (ESCs) in several studies either through embryoid body (EB) formation or by using differentiation medium, and the therapeutic potential of the iPSC-derived cells has also been reported [28][29][30][31][32][33][34][35][36][37][38][39][40][41]. However, no study thus far has reported the in vitro differentiation of iPSCs into BASCs, and the therapeutic potential of BASCs remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Bronchioalveolar Stem Cells Derived from Mouse Induced Pluripotent Stem Cells Promote Airway Epithelium Regeneration

Kawakita

Toba²,

Miyoshi

et al. 2020

Preprint

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Abstract Background: Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.Methods: BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engrafted BASCs on BADJ, and its ability to promote repair an injury to the airway epithelium, were evaluated.Results: Flow cytometric analysis revealed that BASCs represented ~7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs by using transmission electron microscopy showed that the cells containing secretory granules harboured microvilli and small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 d after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs. Conclusions: Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Notably, the differentiated iPSCs promoted airway epithelium at the BADJ in the mouse model of naphthalene-induced airway epithelium injury.

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Effective embryoid body formation from induced pluripotent stem cells for regeneration of respiratory epithelium

Abstract: Based on the varying suspension times and cell numbers with the ALI method, this study presented effective conditions for EB formation from iPS cells for regeneration of respiratory epithelium.

Cited by 7 publications

References 26 publications

Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration

Bronchioalveolar Stem Cells Derived from Mouse Induced Pluripotent Stem Cells Promote Airway Epithelium Regeneration

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