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Acellular Lung Scaffolds Direct Differentiation of Endoderm to Functional Airway Epithelial Cells: Requirement of Matrix-Bound HS Proteoglycans
Open accessAbstract
Efficient differentiation of pluripotent cells to proximal and distal lung epithelial cell populations remains a challenging task. The 3D extracellular matrix (ECM) scaffold is a key component that regulates the interaction of secreted factors with cells during development by often binding to and limiting their diffusion within local gradients. Here we examined the role of the lung ECM in differentiation of pluripotent cells in vitro and demonstrate the robust inductive capacity of the native lung matrix alone. Extended culture of stem cell-derived definitive endoderm on decellularized lung scaffolds in defined, serum-free medium resulted in differentiation into mature airway epithelia, complete with ciliated cells, club cells, and basal cells with morphological and functional similarities to native airways. Heparitinase I, but not chondroitinase ABC, treatment of scaffolds revealed that the differentiation achieved is dependent on heparan sulfate proteoglycans and its bound factors remaining on decellularized scaffolds.
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“Surface proteoglycans that are necessary for successful organoid formation may be removed by harsh decellularization121.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [121]
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Metadata
- Authors
- Shojaie, S., Ermini, L., Ackerley, C., Wang, J., Chin, S., Yeganeh, B., Bilodeau, M., Sambi, M., Rogers, I., Rossant, J., Bear, C. E., & Post, M.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Post, Martin
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 4
- Issue
- 3
- Pages
- 419-430
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4375883
- OpenAlex
- W2012377092
- Cited by
- 102
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 12 · 2022: 10 · 2021: 11 · 2020: 7 · 2019: 15 · 2018: 9 · 2017: 10 · 2016: 11 · 2015: 8
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Use Siena air (University of Siena) (submittedVersion, other-oa)
- 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
- decellularized lung scaffolds, airway epithelial differentiation, definitive endoderm, heparan sulfate proteoglycans, extracellular matrix, ciliated cells, Clara cells, basal cells, stem cell differentiation, lung development, serum-free medium
- MeSH terms
- Thyroid Nuclear Factor 1, Animals, Cell Differentiation, Cells, Cultured, Endoderm, Epithelial Cells, Extracellular Matrix, Lung, Mice, Transgenic, Nuclear Proteins, Protein Binding, Stem Cells, Transcription Factors, Cystic Fibrosis Transmembrane Conductance Regulator, Cell Lineage, Heparan Sulfate Proteoglycans, Respiratory Mucosa, Mice, SOXB1 Transcription Factors, Alveolar Epithelial Cells
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