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demonstrated that there are important differences in ECM composition of decellu-
larized lung tissue from donors with idiopathic pulmonary fibrosis (IPF) compared
to controls (Booth et al. 2012 ). For instance, IPF lungs were enriched in transform-
ing growth factor (TGF)-β-binding protein 1 and depleted in basement membrane
proteins, reflecting the pathological role of TGF-β signaling and loss of epithelial
cell function in IPF. Although it was initially assumed that detergent-mediated
decellularization efficiently removes all cellular material – including non- matrisome
proteins – a recent study by Li and colleagues (Li et al. 2016 ) challenged this notion
by demonstrating the presence of 152 matrisome proteins out of 384 total proteins
in human decellularized lungs. In addition to the possible immunogenicity intro-
duced by non-matrisome proteins in decell-recell bioartificial lungs, this finding
should also be taken into account when interpreting findings from in vitro lung pro-
genitor differentiation on decellularized matrices.
Decellularized lung scaffolds are amenable to a variety of applications from
whole-organ tissue engineering to high-throughput screening of culture conditions
for PSC lung-directed differentiation. Weiss and coworkers first reported the use of
lung tissue slices for in vitro cell culture as an alternative to whole lung decell-recell
Fig. 13.3 Bioengineering platforms for 3D lung differentiation and functional organization –
PSC-derived lung progenitors can be incorporated in various 3D culture systems from decell lung
scaffolds to in vitro derived organoids. The resultant cell structures recapitulate certain functional
and morphological aspects of the native organ. In (b), only a lung multipotent progenitor is shown,
but organoids with varying compositions can be derived by any putative lung stem/progenitor cell
A. Wilson and L. Ikonomou