Development and Bioengineering of Lung Regeneration
The limited ability of the lung to respond to devastating degenerative disease entities provides the impetus to develop new cell-based restorative therapies. Approaches to meet this need could include either production of stem/progenitor cells for deliver
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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 therapies. Approaches to meet this need could include either production of stem/progenitor 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 pathways, a subset of definitive endoderm cells are induced to express Nkx2–1, the earliest 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 transforming the field and are likely both to further our understanding of normal development 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] © Springer Nature Singapore Pte Ltd. 2017 T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology, DOI 10.1007/978-981-10-3768-9_13
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A. Wilson and L. Ikonomou
13.1 Introduction Degenerative lung diseases, such as COPD and pulmonary fibrosis, are both common and a major cause of morbidity and mortality for afflicted patients. In contrast to some other organs or tissues, the various cell types that comprise the lung are largely quiescent at baseline, with a variety of localized stem/progenitor pools maintaining a low turnover index to collectively support tissue homeostasis. In the setting of either acute or chronic degenerative lung disease, these progenitor populations are either unable to regenerate dying cell types, as occurs in emphysema, or respond to injury with an aberrant repair program, as occurs in pulmonary fibrosis or acute interstitial pneumonia (AIP). In each example, the architecture of the lung is damaged in a manner that prevents it from performing its
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