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The effect of age and emphysematous and fibrotic injury on the re-cellularization of de-cellularized lungs

Sokocevic, Dino; Bonenfant, Nicholas R.; Wagner, Darcy E. LU ; Borg, Zachary D.; Lathrop, Melissa J.; Lam, Ying Wai; Deng, Bin; DeSarno, Michael J; Ashikaga, Taka and Loi, Roberto, et al. (2013) In Biomaterials 34(13). p.3256-3269
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... (More)

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.

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type
Contribution to journal
publication status
published
keywords
Acellular matrix, Age, Epithelial cell, Extracellular matrix (ECM), Lung, Mesenchymal stem cell
in
Biomaterials
volume
34
issue
13
pages
3256 - 3269
publisher
Elsevier
external identifiers
  • scopus:84874275434
ISSN
0142-9612
DOI
10.1016/j.biomaterials.2013.01.028
language
English
LU publication?
no
id
5a7798cd-3cf7-44c7-99ea-36313d0cd4af
date added to LUP
2017-08-15 15:09:20
date last changed
2018-08-05 04:43:34
@article{5a7798cd-3cf7-44c7-99ea-36313d0cd4af,
  abstract     = {<p>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.</p>},
  author       = {Sokocevic, Dino and Bonenfant, Nicholas R. and Wagner, Darcy E. and Borg, Zachary D. and Lathrop, Melissa J. and Lam, Ying Wai and Deng, Bin and DeSarno, Michael J and Ashikaga, Taka and Loi, Roberto and Hoffman, Andrew M. and Weiss, Daniel J.},
  issn         = {0142-9612},
  keyword      = {Acellular matrix,Age,Epithelial cell,Extracellular matrix (ECM),Lung,Mesenchymal stem cell},
  language     = {eng},
  number       = {13},
  pages        = {3256--3269},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {The effect of age and emphysematous and fibrotic injury on the re-cellularization of de-cellularized lungs},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2013.01.028},
  volume       = {34},
  year         = {2013},
}