generation-human-3d-lung-tissue-cultures-3d-ltcs-for-disease

Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling

Translation of novel discoveries to human disease is limited by the availability of human tissue-based models of disease. Precision-cut lung slices (PCLS) ...

Lund University

Recent advances in whole lung bioengineering have opened new doors for studying lung repair and regeneration  using acellular human derived lung tissue scaffolds. Methods to decellularise whole human lungs, lobes or resected segments from normal and diseased human lungs have been developed using both perfusion and immersion based techniques. Immersion based techniques allow laboratories without access to intact lobes the ability to generate acellular human lung scaffolds. Acellular human lung scaffolds can be further processed into small segments, thin slices or extracellular matrix extracts, to study cell behaviour such as viability, proliferation, migration and differentiation. Recent studies have offered important proof of concept of generating sufficient primary endothelial and lung epithelial cells to recellularise whole lobes that can be maintained for several days  in a bioreactor to study regeneration. In parallel, acellular human lung scaffolds have been increasingly used for studying cell-extracellular environment interactions. These studies have helped provide new insights into the role of the matrix and the extracellular environment in chronic human lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Acellular human lung scaffolds are a versatile new tool for studying human lung repair and regeneration .

Acellular human lung scaffolds to model lung disease and tissue regeneration.

Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering approaches are exploring the potential to generate lung tissue  for transplantation. Both biologically derived and manufactured scaffolds seeded with cells and grown  have been explored in pre-clinical studies, with the eventual goal of generating functional pulmonary tissue for transplantation. Recently, there have been significant efforts to scale-up cell culture methods to generate adequate cell numbers for human-scale bioengineering approaches. Concomitantly, there have been exciting efforts in designing bioreactors that allow for appropriate cell seeding and development of functional lung tissue over time. This review aims to present the current state-of-the-art progress for each of these areas and to discuss promising new ideas within the field of lung bioengineering.

How to build a lung: latest advances and emerging themes in lung bioengineering.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the lung epithelium are thought to be critical drivers of disease progression, contributing to fibroblast activation, extracellular matrix remodeling, and subsequently loss of lung architecture and function. To date, Pirfenidone and Nintedanib are the only approved drugs known to decelerate disease progression, however, if and how these drugs affect lung epithelial cell function, remains largely unexplored.

Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.

Article	Year
Acellular human lung scaffolds to model lung disease and tissue regeneration. European respiratory review : an official journal of the European Respiratory Society\| PubMed ID: 29875137	2018
How to build a lung: latest advances and emerging themes in lung bioengineering. The European respiratory journal\| PubMed ID: 29903859	2018
Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis. Respiratory research\| PubMed ID: 30219058	2018

Darcy E. Wagner

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