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Generation of 3D Whole Lung Organoids from Induced Pluripotent Stem Cells for Modeling Lung Developmental Biology and Disease
Published on: April 12, 2021
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Embryonic and induced pluripotent stem cells for lung regeneration
Finn Hawkins1, Darrell N Kotton
1Pulmonary Center and Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, Massachusetts.
Annals of the American Thoracic Society
|April 2, 2015
Summary
Scientists can now guide human pluripotent stem cells, including induced pluripotent stem cells (iPSCs), to develop into lung epithelium in vitro. This breakthrough advances regenerative medicine and disease modeling for lung conditions.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Developmental biology
Background:
- Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), offer potential for regenerative medicine.
- Understanding lung development is crucial for treating respiratory diseases.
Purpose of the Study:
- To outline the directed differentiation protocols for generating lung epithelium from hPSCs.
- To highlight the potential of hPSC-derived lung epithelium for disease modeling.
Main Methods:
- Stepwise application of growth factors to guide hPSCs toward lung epithelial lineages.
- Protocols involve inducing definitive endoderm (Activin A), anterior foregut endoderm (BMP and TGF-β inhibition), and lung epithelial specification (Wnt, BMP, FGF signaling).
- Lineage specification is identified by Nkx2.1 expression and subsequent lung epithelial markers.
Main Results:
- Directed differentiation protocols successfully generate lung epithelium from ESCs and iPSCs.
- Generated cells express markers of developing lung and various epithelial subtypes.
- The major limitation remains the derivation and characterization of mature, functional lung epithelium.
Conclusions:
- Directed differentiation of hPSCs is a promising strategy for generating lung epithelium.
- iPSCs from patients with lung diseases provide a valuable platform for disease modeling.
- This approach holds significant potential for advancing regenerative medicine and understanding lung development and disease.
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