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2017 ; 3
(8
): e1700521
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Functional vascularized lung grafts for lung bioengineering
#MMPMID28875163
Dorrello NV
; Guenthart BA
; O'Neill JD
; Kim J
; Cunningham K
; Chen YW
; Biscotti M
; Swayne T
; Wobma HM
; Huang SXL
; Snoeck HW
; Bacchetta M
; Vunjak-Novakovic G
Sci Adv
2017[Aug]; 3
(8
): e1700521
PMID28875163
show ga
End-stage lung disease is the third leading cause of death worldwide, accounting
for 400,000 deaths per year in the United States alone. To reduce the morbidity
and mortality associated with lung disease, new therapeutic strategies aimed at
promoting lung repair and increasing the number of donor lungs available for
transplantation are being explored. Because of the extreme complexity of this
organ, previous attempts at bioengineering functional lungs from fully
decellularized or synthetic scaffolds lacking functional vasculature have been
largely unsuccessful. An intact vascular network is critical not only for
maintaining the blood-gas barrier and allowing for proper graft function but also
for supporting the regenerative cells. We therefore developed an airway-specific
approach to removing the pulmonary epithelium, while maintaining the viability
and function of the vascular endothelium, using a rat model. The resulting
vascularized lung grafts supported the attachment and growth of human adult
pulmonary cells and stem cell-derived lung-specified epithelial cells. We propose
that de-epithelialization of the lung with preservation of intact vasculature
could facilitate cell therapy of pulmonary epithelium and enable bioengineering
of functional lungs for transplantation.