title: The effect of age and emphysematous and fibrotic injury on the re-cellularization of de-cellularized lungs.
abstract: Use of de-cellularized cadaveric lungs as 3-dimensional scaffolds for ex vivo lung tissue generation offers a new potential therapeutic approach for clinical lung transplantation. However, it is likely that some of the available cadaveric human lungs may be from older donors or from donors with previously existing structural lung diseases such as emphysema or pulmonary fibrosis. It is not known whether these lungs will be suitable for either de-cellularization or re-cellularization. To investigate this, we assessed the effects of advanced age, representative emphysematous and fibrotic injuries, and the combination of advanced age and emphysematous injury and found significant differences both in histologic appearance and in the retention of extracellular matrix (ECM) and other proteins, as assessed by immunohistochemistry and mass spectrometry, between the different conditions. However, despite these differences, binding, retention and growth of bone marrow-derived mesenchymal stromal cells (MSCs) over a 1-month period following intratracheal inoculation were similar between the different experimental conditions. In contrast, significant differences occurred in the growth of C10 mouse lung epithelial cells between the different conditions. Therefore, age, lung injury, and the cell type used for re-cellularization may significantly impact the usefulness of de-cellularized whole lungs for ex vivo lung tissue regeneration.
authors: Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA. dino.sokocevic@med.uvm.edu
authors: Dino
authors: D
authors: Sokocevic
authors: Nicholas R
authors: NR
authors: Bonenfant
authors: Darcy E
authors: DE
authors: Wagner
authors: Zachary D
authors: ZD
authors: Borg
authors: Melissa J
authors: MJ
authors: Lathrop
authors: Ying Wai
authors: YW
authors: Lam
authors: Bin
authors: B
authors: Deng
authors: Michael J
authors: MJ
authors: Desarno
authors: Taka
authors: T
authors: Ashikaga
authors: Roberto
authors: R
authors: Loi
authors: Andrew M
authors: AM
authors: Hoffman
authors: Daniel J
authors: DJ
authors: Weiss
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D001761:Bleomycin; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D055370:Lung Injury / Q000150:complications / Q000473:pathology*; D008297:Male; D013058:Mass Spectrometry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000150:complications / Q000473:pathology*
chemical_list: D016326:Extracellular Matrix Proteins; D019394:Ki-67 Antigen; D001761:Bleomycin; D010196:Pancreatic Elastase; D053148:Caspase 3
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