BACKGROUND
As the number of patients with end-stage lung disease continues to rise, there is
a growing need to increase the limited number of lungs available for transplantation.
Unfortunately, attempts at engineering functional lung de novo have been unsuccessful,
and artificial mechanical devices have limited utility as a bridge to transplant.
This difficulty is largely due to the size and inherent complexity of the lung; however,
recent advances in cell-based therapeutics offer a unique opportunity to enhance traditional
tissue-engineering approaches with targeted site- and cell-specific strategies.
METHODS
Human lungs considered unsuitable for transplantation were procured and supported
using novel cannulation techniques and modified ex-vivo lung perfusion. Targeted lung
regions were treated using intratracheal delivery of decellularization solution. Labeled
mesenchymal stem cells or airway epithelial cells were then delivered into the lung
and incubated for up to 6 hours.
RESULTS
Tissue samples were collected at regular time intervals and detailed histologic and
immunohistochemical analyses were performed to evaluate the effectiveness of native
cell removal and exogenous cell replacement. Regional decellularization resulted in
the removal of airway epithelium with preservation of vascular endothelium and extracellular
matrix proteins. After incubation, delivered cells were retained in the lung and showed
homogeneous topographic distribution and flattened cellular morphology.
CONCLUSIONS
Our findings suggest that targeted cell replacement in extracorporeal organs is feasible
and may ultimately lead to chimeric organs suitable for transplantation or the development
of in-situ interventions to treat or reverse disease, ultimately negating the need
for transplantation.
Keywords
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Article info
Publication history
Published online: November 21, 2018
Identification
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© 2018 International Society for Heart and Lung Transplantation. All rights reserved.
