Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling
Open accessAbstract
Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology. This is specifically true of lung diseases where animal models often do not recapitulate human disease. Here, we present a method for the generation of self-assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis (IPF). Tissue formation occurs because of the overlapping processes of cellular adhesion to multiple alveolar sac templates, bioreactor rotation, and cellular contraction. Addition of transforming growth factor-β1 to single cell-type mesenchymal organoids resulted in morphologic scarring typical of that seen in IPF but not in two-dimensional IPF fibroblast cultures. Furthermore, this lung organoid may be modified to contain multiple lung cell types assembled into the correct anatomical location, thereby allowing cell-cell contact and recapitulating the lung microenvironment. Our bottom-up approach for synthesizing patient-specific lung tissue in a scalable system allows for the development of relevant human lung disease models with the potential for high throughput drug screening to identify targeted therapies.
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Organoid types grown in alginate include human lung, human brain, murine intestinal, human intestinal, human pancreatic, and human and murine vascular.
“Organoid types grown in alginate include human lung99,100, human brain101, murine intestinal102, human intestinal102,103, human pancreatic104, and human and murine vascular105.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [99]
Several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.
“In addition to organoids grown in naturally-derived proteins, several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [99]
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- Authors
- Wilkinson, D. C., Alva-Ornelas, J. A., Sucre, J. M. S., Vijayaraj, P., Durra, A., Richardson, W., Jonas, S. J., Paul, M. K., Karumbayaram, S., Dunn, B., & Gomperts, B. N.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Gomperts, Brigitte N.
- ORCID
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-09-15
- Volume
- 6
- Issue
- 2
- Pages
- 622-633
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- PMC
- PMC5442826
- OpenAlex
- W2520176498
- Cited by
- 165
- References
- 36
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 11 · 2023: 21 · 2022: 28 · 2021: 24 · 2020: 14 · 2019: 8 · 2018: 19 · 2017: 15 · 2016: 2
- FWCI
- 16.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cells Translational Medicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation
- California Institute for Regenerative Medicine (12-02)
- National Institutes of Health
- University of California, Los Angeles
- National Institute of General Medical Sciences (GM114259-01, R01GM114259)
- Jonsson Comprehensive Cancer Center
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- lung organoids, idiopathic pulmonary fibrosis, disease modeling, TGF-β1, fibrosis, drug screening, personalized medicine, organ regeneration
- MeSH terms
- Cell Differentiation, Cells, Cultured, Fibroblasts, Humans, Lung, Organoids, Phenotype, Time Factors, Cell Culture Techniques, Cell Lineage, Bioreactors, Tissue Engineering, Transforming Growth Factor beta1, Idiopathic Pulmonary Fibrosis, Induced Pluripotent Stem Cells
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