Comparative decellularization and recellularization of normal versus emphysematous human lungs.
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.
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Darcy E
DE
Wagner
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Nicholas R
NR
Bonenfant
Department of Surgery, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Charles S
CS
Parsons
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Dino
D
Sokocevic
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Elice M
EM
Brooks
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Zachary D
ZD
Borg
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Melissa J
MJ
Lathrop
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
John D
JD
Wallis
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA.
Amanda B
AB
Daly
Department of Biology, University of Vermont, 311 Marsh Life Sciences, Burlington, VT 05405, USA.
Ying Wai
YW
Lam
Department of Biology, University of Vermont, 311 Marsh Life Sciences, Burlington, VT 05405, USA.
Bin
B
Deng
Department of Biostatistics, University of Vermont, 27 Hills Building, Burlington, VT 05405, USA.
Michael J
MJ
DeSarno
Department of Biostatistics, University of Vermont, 27 Hills Building, Burlington, VT 05405, USA.
Takamaru
T
Ashikaga
Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Roberto
R
Loi
Department of Medicine, University of Vermont, College of Medicine, 226 Health Science Research Facility, Burlington, VT 05405, USA. Electronic address: dweiss@uvm.edu.
Daniel J
DJ
Weiss
D002460:Cell Line; D004646:Emphysema / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology*; D013058:Mass Spectrometry; D008854:Microscopy, Electron
D016326:Extracellular Matrix Proteins
Acellular matrix; Emphysema; Endothelial cell; Epithelial cell; Extracellular matrix (ECM); Human lung fibroblast