Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties
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Abstract
Tissues derived from human pluripotent stem cells (hPSCs) often represent early stages of fetal development, but mature at the molecular and structural level when transplanted into immunocompromised mice. hPSC-derived lung organoids (HLOs) transplantation has been further enhanced with biomaterial scaffolds, where HLOs had improved tissue structure and cellular differentiation. Here, our goal was to define the physico-chemical biomaterial properties that maximally enhanced transplant efficiency, including features such as the polymer type, degradation, and pore interconnectivity of the scaffolds. We found that transplantation of HLOs on microporous scaffolds formed from poly (ethylene glycol) (PEG) hydrogel scaffolds inhibit growth and maturation, and the transplanted HLOs possessed mostly immature lung progenitors. On the other hand, HLOs transplanted on poly (lactide-co-glycolide) (PLG) scaffolds or polycaprolactone (PCL) led to tube-like structures that resembled both the structure and cellular diversity of an adult airway. Our data suggests that scaffold pore interconnectivity and polymer degradation contributed to the maturation, and we found that the size of the airway structures and the total size of the transplanted tissue was influenced by the material degradation rate. Collectively, these biomaterial platforms provide a set of tools to promote maturation of the tissues and to control the size and structure of the organoids.
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Human lung organoids transplanted in mice could merge together to form airway structures, but only if the scaffold was able to degrade, which increased the material's pore size.
“Dye and coworkers found that human lung organoids transplanted in mice could merge together to form airway structures. However, this was only possible if the scaffold was able to degrade, which increased the material’s pore size135.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [135]
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- Authors
- Dye, B. R., Youngblood, R. L., Oakes, R. S., Kasputis, T., Clough, D. W., Spence, J. R., & Shea, L. D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Spence, Jason R.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 234
- Pages
- 119757
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC6996062
- OpenAlex
- W2997229843
- Cited by
- 75
- References
- 45
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 11 · 2023: 10 · 2022: 14 · 2021: 15 · 2020: 8
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Biomaterials (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- airway maturation, biomaterial scaffolds, polymer degradation, poly(lactic-co-glycolic acid), polycaprolactone, poly(ethylene glycol) hydrogels, organoid transplantation, lung progenitor cells, tissue engineering
- MeSH terms
- Adult, Animals, Biocompatible Materials, Humans, Infant, Newborn, Lung, Organoids, Hydrogels, Tissue Engineering, Pluripotent Stem Cells, Mice, Tissue Scaffolds
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