Modeling human lung development and disease using pluripotent stem cells

Snoeck, Hans-Willem

doi:10.1242/dev.115469

Cited by 43 publications

(28 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, an in vitro experimental model of lung branching morphogenesis with secondary and tertiary branch formation is strongly needed for studies of lung development and disease. 16,17 …”

Section: Introductionmentioning

confidence: 99%

In VitroExperimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells

Hagiwara

Maruta

Marumoto

2017

Tissue Engineering Part C: Methods

View full text Add to dashboard Cite

Lung branching morphogenesis has been studied for decades, but the underlying developmental mechanisms are still not fully understood. Cellular movements dynamically change during the branching process, but it is difficult to observe long-term cellular dynamics by in vivo or tissue culture experiments. Therefore, developing an in vitro experimental model of bronchial tree would provide an essential tool for developmental biology, pathology, and systems biology. In this study, we succeeded in reconstructing a bronchial tree in vitro by using primary human bronchial epithelial cells. A high concentration gradient of bronchial epithelial cells was required for branching initiation, whereas homogeneously distributed endothelial cells induced the formation of successive branches. Subsequently, the branches grew in size to the order of millimeter. The developed model contains only two types of cells and it facilitates the analysis of lung branching morphogenesis. By taking advantage of our experimental model, we carried out long-term time-lapse observations, which revealed self-assembly, collective migration with leader cells, rotational motion, and spiral motion of epithelial cells in each developmental event. Mathematical simulation was also carried out to analyze the self-assembly process and it revealed simple rules that govern cellular dynamics. Our experimental model has provided many new insights into lung development and it has the potential to accelerate the study of developmental mechanisms, pattern formation, left–right asymmetry, and disease pathogenesis of the human lung.

show abstract

Section: Introductionmentioning

confidence: 99%

In VitroExperimental Model for the Long-Term Analysis of Cellular Dynamics During Bronchial Tree Development from Lung Epithelial Cells

Hagiwara

Maruta

Marumoto

2017

Tissue Engineering Part C: Methods

View full text Add to dashboard Cite

show abstract

“…This is still a real challenge for the field [see, for example, the discussion on generating lung cells elsewhere in this issue (Snoeck et al, 2015)]. In part, this reflects the fact that these stages tend to show more variation among species.…”

Section: Introductionmentioning

confidence: 99%

Mouse and human blastocyst-derived stem cells: vive les differences

Rossant

2015

Development

118

View full text Add to dashboard Cite

Lessons learned from conserved vertebrate developmental pathways have catalyzed rapid advances in pluripotent stem cell differentiation towards therapeutically relevant cell types. The most highly conserved phases of development are associated with the early patterning of the body plan -the so-called phylotypic stage. Both prior to and after this stage there is much more divergence across species. Developmental differences between human and mouse at the blastocyst and early post-implantation stages might help explain the differences among the different stem cell lines derived from these embryos. A better understanding of these early stages of human development will aid our ability to generate and manipulate human stem cells and their derivatives.

show abstract

“…Janet Rossant discusses key differences between early mouse and human development, and how these relate to the ability to derive different stem cell lines from these embryos (Rossant, 2015). Looking at much later stages of development, Hans-Willem Snoeck explains, using the lung as an example, why it is essential to understand human development if we are to make progress in treating disease (Snoeck, 2015). Although the potential of human stem cell research is immense, it does raise a number of important ethical issues, and Göran Hermerén and Insoo Hyun, *Author for correspondence ( pourquieeicdev@igbmc.fr) who led a discussion session on ethics at the workshop, discuss some of the ethical considerations of working with human stem cells, with a particular focus on the ethics of generating humananimal chimeras (Hermerén, 2015;Hyun, 2015).…”

mentioning

confidence: 99%