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Comparative decellularization and recellularization of normal versus emphysematous human lungs

Wagner, Darcy E. LU ; Bonenfant, Nicholas R.; Parsons, Charles S.; Sokocevic, Dino; Brooks, Elice M.; Borg, Zachary D.; Lathrop, Melissa J.; Wallis, John D.; Daly, Amanda B. and Lam, Ying Wai, et al. (2014) In Biomaterials 35(10). p.3281-3297
Abstract

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... (More)

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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publication status
published
keywords
Acellular matrix, Emphysema, Endothelial cell, Epithelial cell, Extracellular matrix (ECM), Human lung fibroblast
in
Biomaterials
volume
35
issue
10
pages
3281 - 3297
publisher
Elsevier
external identifiers
  • scopus:84893652193
ISSN
0142-9612
DOI
10.1016/j.biomaterials.2013.12.103
language
English
LU publication?
no
id
5c929902-5000-439f-8f8d-d441da35d1aa
date added to LUP
2017-08-15 15:07:25
date last changed
2017-10-08 05:06:02
@article{5c929902-5000-439f-8f8d-d441da35d1aa,
  abstract     = {<p>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.</p>},
  author       = {Wagner, Darcy E. and Bonenfant, Nicholas R. and Parsons, Charles S. and Sokocevic, Dino and Brooks, Elice M. and Borg, Zachary D. and Lathrop, Melissa J. and Wallis, John D. and Daly, Amanda B. and Lam, Ying Wai and Deng, Bin and DeSarno, Michael J and Ashikaga, Takamaru and Loi, Roberto and Weiss, Daniel J.},
  issn         = {0142-9612},
  keyword      = {Acellular matrix,Emphysema,Endothelial cell,Epithelial cell,Extracellular matrix (ECM),Human lung fibroblast},
  language     = {eng},
  number       = {10},
  pages        = {3281--3297},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {Comparative decellularization and recellularization of normal versus emphysematous human lungs},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2013.12.103},
  volume       = {35},
  year         = {2014},
}