Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells

Konishi, Satoshi; Gotoh, Shimpei; Tateishi, Kazuhiro; Yamamoto, Yuki; Korogi, Yukunori; Nagasaki, Tadao; Matsumoto, Hisako; Muro, Shigeo; Hirai, Toyohiro; Ito, Isao; Tsukita, Sachiko; Mishima, Michiaki

doi:10.1016/j.stemcr.2015.11.010

Cited by 213 publications

(249 citation statements)

References 34 publications

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“…To date, several groups have derived two and three-dimensional lung models from both primary human lung tissue and from hPSCs that consist of airway epithelial cell types (Barkauskas et al, 2013; Rock et al, 2009; Gotoh et al., 2014; Konishi et al, 2016; Dye et al, 2015; Firth et al, 2014; Mou et al, 2016; Wong et al., 2012; Huang et al, 2013). Tissue grown on an air-liquid interface generated an organized pseudostratified epithelium that reflects most of the cellular diversity of the human airway (Mou et al, 2016; Wong et al., 2012), while other models possess an airway epithelium with a supporting mesenchyme (Firth et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…These advances stem from our ability to culture primary human tissues and derive complex three-dimensional organ-like tissues, called organoids from human pluripotent stem cells (hPSCs) (Dedhia et al, 2016; Fatehullah et al, 2016; Johnson and Hockemeyer, 2015; Huch and Koo, 2015; Rookmaaker et al, 2015; Dye et al, 2016). Both tissue-derived and hPSC-derived human lung models have been developed and recapitulate some structural and cellular features of the human lung (Barkauskas et al, 2013; Rock et al, 2009; Gotoh et al., 2014; Konishi et al, 2016; Vaughan et al, 2006; Pageau et al, 2011; Fessart et al, 2013; Franzdóttir et al, 2010; Kaisani et al, 2014; Dye et al, 2015; Firth et al, 2014; Mou et al, 2016). For example, we recently described methods to direct differentiation of hPSCs in a stepwise process, which mimicked aspects of in vivo lung development, into three-dimensional human lung organoids (HLOs).…”

Section: Introductionmentioning

confidence: 99%

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A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

Dye

Dedhia

Miller

et al. 2016

eLife

166

197

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Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (Dye et al., 2015). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung.DOI: http://dx.doi.org/10.7554/eLife.19732.001

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

Dye

Dedhia

Miller

et al. 2016

eLife

166

197

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“…[112,[119][120][121][122][123][124][125] Recently, a cell surface marker specific to NKX2.1+ lung progenitors was discovered and used to sort out NKX2.1+ lung progenitors from hPSC-derived lung cultures using flow cytometry. [126,127] The single cells were placed in a Matrigel droplet overlaid with airway-specific media, which resulted in airway cysts that contain basal cells and a few other mature epithelial airway cells. [126] Both the hPSC and primary basal cell airway cysts contain a single layer of epithelial cells that contained basal cells and other mature airway cells.…”

Section: Airway Organoidsmentioning

confidence: 99%

“…[126,127] The single cells were placed in a Matrigel droplet overlaid with airway-specific media, which resulted in airway cysts that contain basal cells and a few other mature epithelial airway cells. [126] Both the hPSC and primary basal cell airway cysts contain a single layer of epithelial cells that contained basal cells and other mature airway cells. [112,[119][120][121][122][123][124]126] Airway models have also been derived from a cluster of hPSC-derived lung progenitors and mesenchymal cells referred to as lung spheroids.…”

Section: Airway Organoidsmentioning

confidence: 99%

“…[126] Both the hPSC and primary basal cell airway cysts contain a single layer of epithelial cells that contained basal cells and other mature airway cells. [112,[119][120][121][122][123][124]126] Airway models have also been derived from a cluster of hPSC-derived lung progenitors and mesenchymal cells referred to as lung spheroids. [128,129] These lung spheroids were derived similar to hPSC-derived intestinal organoids that relied on growth factor stimulated self-assembly to induce spheroid formation from the endodermal monolayer.…”

Section: Airway Organoidsmentioning

confidence: 99%

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Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

et al. 2017

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Human organoid models recapitulate many aspects of the complex composition and function of native organs. One of the main challenges in developing these models is the growth and maintenance of three-dimensional tissue structures and proper cellular organization that enable function. Biomaterials play an important role by providing a defined and tunable three-dimensional environment that is required for complex cellular organization and organoid growth in vitro or in vivo. This review summarizes organoids of the respiratory and digestive system, and the use of biomaterials to improve upon these model systems.

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Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells

Moreira¹,

Müller

Costa³

et al. 2021

Advanced Biology

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Respiratory diseases are among the global leading causes of morbidity and mortality. Acute conditions arising from infection, such as pneumonia and tuberculosis, affect millions of people worldwide, the latter being the most common lethal infectious disease with 1.4 million annual deaths. [1] Upon infection, the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused a worldwide pandemic, leads to the clinical picture of the coronavirus disease-2019 (COVID-19) with possibly severe and life-threatening progression. Lung cancer is the most frequently diagnosed malignancy and the main cause of cancer-related death, [2] with markedly low survival rates especially when the diagnosis is performed at an advanced state of the disease. [3] Moreover, chronic respiratory diseases (CRDs), including chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung disease (ILD), have consistently received less attention in comparison to other non-communicable diseases, continuing to exert a considerable socioeconomic impact. [4,5] Risk factors for the development of respiratory diseases include, for example, tobacco use and second-hand smoke, as well as exposure to air-pollutants, which has been accentuated with the widespread use of fossil fuels. [4] It is clear that a great number of these risks can be mitigated by lifestyle changes, promoted by anti-tobacco campaigns already in place at a global scale and by the use of renewable, clean energy sources, and two recent studies indicate that the age-standardized incidence and prevalence of CRDs has decreased from 1990 to 2017. [4,5] However, the risk of developing CRDs, particularly COPD, appears to increase steeply with age; [4,5] most strikingly, these diseases were the third leading cause of death in 2017 [4] and potentially in 2020. [6] In addition to microbial, environmental, and lifestyle-related factors, a large number of lung diseases have a genetic origin. [7] Cystic fibrosis (CF), for example, is an incurable hereditary disorder known to originate from different mutations in the gene coding for the CF transmembrane conductance regulator (CFTR), an ion transporter, resulting in severe alterations in pulmonary physiology that culminate in impaired lung function, respiratory distress and, ultimately, death. [8,9]

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Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells

Cited by 213 publications

References 34 publications

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells

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