Chapter 74 – Lungs

Pulmonary regenerative medicine and tissue engineering is a rapidly expanding field combining the core elements of stem cell biology, scaffold engineering, and design of multifaceted cell culture systems and bioreactors. Methods for derivation of lung epithelial cell lineages from embryonic stem cells have been established and are currently being refined; the existence of multipotent adult human lung stem cells that give rise to epithelial and vascular tissue has been reported. The absence of literature regarding derivation of lung-specific vascular and mesenchymal lineages presents a challenge moving forward. Methods of implementation and therapeutic efficacy of stem cell-derived distal pulmonary cell populations in animal models of human lung disease remain to be determined. The current ‘state of the art' for high-fidelity complex scaffolding in lung tissue engineering is the use of decellularized cadaveric lungs, which provides a unique platform for whole lung organ engineering. This approach allows for preservation of the intricate lung architecture that may be subsequently recellularized via perfusion through both the airway and vascular conduits. Implementation of engineered scaffolds from other sources will require methods that capture the unique architectural and mechanical properties of the lung. A major advance in the field has been the development of bioreactor systems capable of simultaneous airway ventilation and vascular perfusion of tissue-engineered lungs created using decellularized lung scaffolds. Scale-up of these systems to larger animal models and eventually humans, as well as the potential of lingering immunogenicity and availability of healthy cadaveric tissue remain major challenges facing this paradigm. Other key areas of research discussed in this chapter include the development of stem cell bioprocessing systems and microfluidic ‘lung-on-a-chip' devices that provide a novel platform for high throughput testing of pharmaceuticals.