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Updated: Mar 14, 2026
Generation of 3D Whole Lung Organoids from Induced Pluripotent Stem Cells for Modeling Lung Developmental Biology and Disease
Published on: April 12, 2021
Organogenesis of adult lung in a dish: Differentiation, disease and therapy
Jinwook Choi1, Elhadi Iich1, Joo-Hyeon Lee2
1Wellcome Trust/Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Abstract:
The remarkable regenerative capacity of the lung suggests that stem cells could be of therapeutic importance in diverse lung diseases; however, the successful exploitation of lung stem cell biology has long been hampered by our inability to maintain and expand adult lung stem cells while retaining their multi-lineage potential in vitro. Recently, advances in our understanding of stem cell niches and the role of key signalling modulators in controlling stem cell maintenance and differentiation have fuelled the development of new in vitro three-dimensional (3D) culture technologies that sustain the stem cell-driven formation of near-physiological, self-organizing structures called organoids. Here we review basic approaches to organoid model systems and highlight recent achievements in the generation of organoids from adult stem and progenitor cells of both the murine and human lungs. We evaluate current applications in studying cellular changes in proliferation, differentiation, plasticity, and cell polarity, and cellular and molecular crosstalk of epithelial cells with stroma. Advantages and limitations of organoids for clinical use are also discussed.
Insights
Lung stem cell organoids offer new therapeutic potential for lung diseases. These 3D models maintain stem cell properties in vitro, aiding research into lung regeneration and disease treatment.
Area of Science:
- Pulmonary Medicine
- Stem Cell Biology
- Regenerative Medicine
Background:
- Lung stem cells hold therapeutic promise for diverse lung diseases due to their regenerative capacity.
- In vitro expansion of adult lung stem cells while preserving multi-lineage potential has been a significant challenge.
- Recent advances in understanding stem cell niches and signaling pathways have enabled new culture technologies.
Purpose of the Study:
- To review organoid model systems for lung stem cells.
- To highlight achievements in generating murine and human lung organoids.
- To evaluate organoid applications and clinical potential.
Main Methods:
- Development of in vitro three-dimensional (3D) culture technologies.
- Utilizing advances in stem cell niche understanding and signaling modulators.
- Generating organoids from adult stem and progenitor cells of murine and human lungs.
Main Results:
- Successful generation of near-physiological, self-organizing lung organoids from adult stem and progenitor cells.
- Organoids sustain stem cell-driven formation and multi-lineage potential in vitro.
- Evaluation of organoid applications in studying cellular proliferation, differentiation, plasticity, and cell-cell crosstalk.
Conclusions:
- Lung organoids represent a significant advancement for studying lung stem cell biology in vitro.
- These models offer valuable insights into cellular dynamics and cell-stroma interactions.
- Organoids show promise for clinical applications in lung disease research and therapy, despite current limitations.
