Generation of Lung Epithelium from Pluripotent Stem Cells

Wong, Amy P.; Rossant, Janet

doi:10.1007/s40139-013-0016-9

Cited by 22 publications

(23 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During fetal development in mouse and human, the foregut endoderm begins to form lung buds, which further undergo stereotypical branching morphogenesis . The initial epithelium is composed of proximal progenitors, including basal cells, which closely adhere to the basal lamina.…”

Section: Epithelial Cells In the Lungmentioning

confidence: 99%

“…50% “pure,” and sometimes substantially less. The actual pathway for differentiating iPSCs to definitive adult lung epithelial cells is full of many zigs and zags, well summarized in the review by Wong and Rossant . Thus the in vitro proof‐of‐principal example given in the introduction represents more of a beginning than an end.…”

Section: Ipscs To Rescue Cf Lung Diseasementioning

confidence: 99%

“…However, there are clinical, structural, and physiologic barriers which must be overcome to move from these in vitro proof‐of‐principle experiments to deploying the technology therapeutically in CF patients. Many outstanding articles and comprehensive reviews have been published in the last few years that specifically address the lung . Here, we will assess important challenges that the lung, and the CF disease itself, erects against different therapeutic strategies.…”

Section: Introduction: the Ipsc Promise For Repairing The Cystic Fibrmentioning

confidence: 99%

See 2 more Smart Citations

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Pollard¹,

Pollard

2018

Pediatric Pulmonology

View full text Add to dashboard Cite

Induced pluripotent stem cells (iPSCs) are a recently developed technology in which fully differentiated cells such as fibroblasts from individual CF patients can be repaired with [wildtype] CFTR, and reprogrammed to differentiate into fully differentiated cells characteristic of the proximal and distal airways. Here, we review properties of different epithelial cells in the airway, and the in vitro genetic roadmap which iPSCs follow as they are step-wise differentiated into either basal stem cells, for the proximal airway, or into Type II Alveolar cells for the distal airways. The central theme is that iPSC-derived basal stem cells, are penultimately dependent on NOTCH signaling for differentiation into club cells, goblet cells, ciliated cells, and neuroendocrine cells. Furthermore, given the proper matrix, these cellular progenies are also able to self-assemble into a fully functional pseudostratified squamous proximal airway epithelium. By contrast, club cells are reserve stem cells which are able to either differentiate into goblet or ciliated cells, but also to de-differentiate into basal stem cells. Variant club cells, located at the transition between airway and alveoli, may also be responsible for differentiation into Type II Alveolar cells, which then differentiate into Type I Alveolar cells for gas exchange in the distal airway. Using gene editing, the mutant CFTR gene in iPSCs from CF patients can be repaired, and fully functional epithelial cells can thus be generated through directed differentiation. However, there is a limitation in that the lung has other CFTR-dependent cells besides epithelial cells. Another limitation is that there are CFTR-dependent cells in other organs which would continue to contribute to CF disease. Furthermore, there are also bystander or modifier genes which affect disease outcome, not only in the lung, but specifically in other CF-affected organs. Finally, we discuss future personalized applications of the iPSC technology, many of which have already survived the "proof-of-principle" test. These include (i) patient-derived iPSCs used as a "lung-on-a-chip" tool for personalized drug discovery; (ii) replacement of mutant lung cells by wildtype lung cells in the living lung; and (iii) development of bio-artificial lungs. It is hoped that this review will give the reader a roadmap through the most complicated of the obstacles, and foster a guardedly optimistic view of how some of the remaining obstacles might one day be overcome.

show abstract

Section: Epithelial Cells In the Lungmentioning

confidence: 99%

Section: Ipscs To Rescue Cf Lung Diseasementioning

confidence: 99%

Section: Introduction: the Ipsc Promise For Repairing The Cystic Fibrmentioning

confidence: 99%

See 1 more Smart Citation

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Pollard¹,

Pollard

2018

Pediatric Pulmonology

View full text Add to dashboard Cite

show abstract

“…Большие надежды в этом плане возлагаются на методы клеточной терапии, которые могли бы предотвратить образование соединительной рубцовой ткани вместо мышечной. Простейшим подходом к решению этой задачи могло бы быть перепрограммирование сердечных фибробластов непосредственно в организме путем доставки в сердце факторов транскрипции [53] или микроРНК [54][55]. Была предпринята попытка перепрограммировать сердечные фибробласты в кардиомиоцит-подобные клетки in vivo путем гиперэкспрессии в них факторов транскрипции Gata4, Mef2c и Tbx5 (GMT) [56].…”

Section: рис 2 механизмы эпителиально-мезенхимного переходаunclassified

Epithelial-mesenchymal transition, transdifferentiation, reprogramming and metaplasia: modern view on the problem

Мнихович¹,

Vernigorodsky²,

Буньков³

2017

MV-MN

View full text Add to dashboard Cite

“…78 Once generated, iPS cells can be differentiated either into endoderm cells, the precursors for lung and liver tissues, 83,84 and can subsequently be differentiated further into lung epithelial cells. 85 The differentiation of ES or iPS cells into a bronchial epithelium has recently been achieved. 86 However, cultures were not homogeneous and also contained SP-C expressing (function specic to ATII cells) cells, although co-localisation of both bronchial and alveolar cells does not occur.…”

Section: Primary Cellsmentioning

confidence: 99%

Modelling the Human Respiratory System: Approaches forin VitroSafety Testing and Drug Discovery

Prytherch¹,

Bérubé²

2014

Human-Based Systems for Translational Research

View full text Add to dashboard Cite

Respiratory research can be broken down into two main areas: (i) exposure to airborne substances (basic toxicology assessment); and (ii) respiratory diseases (understanding disease mechanisms and development of new therapeutics, including toxicological assessment). Both have suffered from inadequate and inaccurate models used to predict human toxicological end points. A growing need therefore exists for accurate in vitro models of the respiratory system, which accurately reflect the human lung situation in vivo. Advances in cell culture techniques and accessibility of human cells/tissues have resulted in the development of increasingly in vivo-like respiratory models. This chapter will focus on the development, advantages and disadvantages of these models and what the future holds for in vitro lung toxicology.

show abstract

Generation of Lung Epithelium from Pluripotent Stem Cells

Cited by 22 publications

References 83 publications

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Induced pluripotent stem cells for treating cystic fibrosis: State of the science

Epithelial-mesenchymal transition, transdifferentiation, reprogramming and metaplasia: modern view on the problem

Modelling the Human Respiratory System: Approaches forin VitroSafety Testing and Drug Discovery

Contact Info

Product

Resources

About