© Springer Nature Singapore Pte Ltd. 2017 237
T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology,
DOI 10.1007/978-981-10-3768-9_13
Chapter 13
Development and Bioengineering of Lung
Regeneration
Andrew Wilson and Laertis Ikonomou
Abstract The limited ability of the lung to respond to devastating degenerative
disease entities provides the impetus to develop new cell-based restorative thera-
pies. Approaches to meet this need could include either production of stem/progeni-
tor cells for delivery to the damaged native lung to regenerate damaged tissue or
engineering of a de novo transplantable organ. In either case, an understanding of
normal lung development provides a road map for directing pluripotent stem cells
(PSCs) to differentiate to lung epithelium in vitro. Lung epithelium is derived from
the endodermal germ layer, which in turn is formed during gastrulation as cells
migrate through the primitive streak. Through precisely coordinated temporospatial
exposure to key agonists and antagonists of the WNT, FGF, BMP, and RA path-
ways, a subset of definitive endoderm cells are induced to express Nkx2–1, the earli-
est known marker of primordial lung progenitor cells, before further differentiation
to mature cell types comprising the proximal and distal lung compartments. Novel
culture systems, such as decellularized lung scaffolds and in vitro organoids, offer
unprecedented opportunities for achieving multilineage differentiation and tissue-
like structure formation together with functional evaluation of PSC-derived lung
progenitors. Combined with advances in our ability to model lung development
in vitro with human PSCs, emerging bioengineering techniques are rapidly trans-
forming the field and are likely both to further our understanding of normal develop-
ment and to facilitate therapeutic applications of these in the years to come.
Keywords Development • Stem cells • Directed differentiation • NKX2–1 •
Decellularization-recellularization • Lung scaffolds • Organoids • 3D bioprinting •
Bioartificial lung
A. Wilson • L. Ikonomou (*)
Center for Regenerative Medicine (CReM) of Boston University
and Boston Medical Center, Boston, MA, USA
e-mail: [email protected]; [email protected]