Comparative decellularization and recellularization of normal versus emphysematous human lungs

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Darcy E. Wagner
  • Nicholas R. Bonenfant
  • Charles S. Parsons
  • Dino Sokocevic
  • Elice M. Brooks
  • Zachary D. Borg
  • Melissa J. Lathrop
  • John D. Wallis
  • Amanda B. Daly
  • Ying Wai Lam
  • Bin Deng
  • Michael J DeSarno
  • Takamaru Ashikaga
  • Roberto Loi
  • Daniel J. Weiss
External organisations
  • University of Vermont
  • University of Cagliari
Research areas and keywords

Keywords

  • Acellular matrix, Emphysema, Endothelial cell, Epithelial cell, Extracellular matrix (ECM), Human lung fibroblast
Original languageEnglish
Pages (from-to)3281-3297
JournalBiomaterials
Volume35
Issue number10
Publication statusPublished - 2014 Mar
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes