Comparative decellularization and recellularization of normal versus emphysematous human lungs
Open accessAbstract
Acellular whole human lung scaffolds represent a unique opportunity for ex vivo tissue engineering. However, it remains unclear whether lungs from individuals with chronic lung diseases such as chronic obstructive pulmonary disease (COPD) can be appropriately decellularized and recellularized. To assess this, cadaveric human lungs from normal (non-smoking) patients and from patients with COPD (smoking history) were decellularized and found by histochemical and immunohistochemical staining, electron microscopy, and mass spectrometry to retain characteristic histological architecture and extracellular matrix components (ECM) reflecting either normal or COPD, particularly emphysematous, origin. Inoculation of human bronchial epithelial cells, endothelial progenitor cells, bone marrow-derived mesenchymal stem cells, and lung fibroblasts via airway or vascular routes into small, excised segments of the decellularized lungs demonstrated that normal lung scaffolds robustly supported initial engraftment and growth of each cell type for up to one month. In contrast, despite initial binding, all cell types inoculated into decellularized emphysematous lungs did not survive beyond one week. However, cell attachment and proliferation on solubilized ECM homogenates of decellularized normal and emphysematous lungs coated onto tissue culture plates was comparable and not impaired, suggesting that the 3-dimensional decellularized emphysematous scaffolds may lack the necessary ECM architecture to support sustained cell growth.
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Alterations in emphysematous or fibrotic lung tissue can lead to cells failing to survive beyond one week of culture or broad changes in the phenotype of seeded cells that do survive.
“These alterations can lead to cells failing to survive beyond one week of culture118 or broad changes in the phenotype of seeded cells that do survive119.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [118]
Emphysematous or fibrotic lung tissue has hardened and undergone alterations in its architecture.
“For example, emphysematous or fibrotic lung tissue has hardened and undergone alterations in its architecture.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [118]
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- Authors
- Wagner, D. E., Bonenfant, N. R., Parsons, C. S., Sokocevic, D., Brooks, E. M., Borg, Z. D., Lathrop, M. J., Wallis, J. D., Daly, A. B., Lam, Y. W., Deng, B., DeSarno, M. J., Ashikaga, T., Loi, R., & Weiss, D. J.
- Affiliations
- University of Vermont (US)
- University of Cagliari (IT)
- Corresponding author
- Weiss, Daniel J.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 35
- Issue
- 10
- Pages
- 3281-3297
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC4215725
- OpenAlex
- W2086166247
- Cited by
- 172
- References
- 27
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 8 · 2023: 14 · 2022: 11 · 2021: 23 · 2020: 14 · 2019: 10 · 2018: 16 · 2017: 14 · 2016: 17 · 2015: 21 · 2014: 13
- FWCI
- 21.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- NIH (ARRA RC4HL106625, NHLBI R21HL094611, 8P20GM103449)
- NHLBI (T32 HL076122)
- NIEHS (T32 ES007122)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- decellularization, recellularization, emphysema, chronic obstructive pulmonary disease, extracellular matrix, cell engraftment, bronchial epithelial cells, endothelial progenitor cells, mesenchymal stem cells, lung fibroblasts, cell adhesion and proliferation
- MeSH terms
- Cell Line, Emphysema, Humans, Lung, Microscopy, Electron, Mass Spectrometry, Extracellular Matrix Proteins
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