Lung and Airway Engineering

Updated: May 10

Chronic respiratory diseases remain a significant cause of morbidity and mortality worldwide. The only option for an end-stage illness is lung transplantation, but there are not enough donors to address the clinical demand. Consequently, a growing number of tissue engineering approaches explore the potential to generate lung and airway tissue ex vivo, replacing the traditional lung and airways transplantation [1]. These developing technologies of lung tissue engineering have also helped treat some pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and congenital lung hypoplasia [2].


Recent studies have demonstrated the viability of decellularizing the whole organ by removing all its cellular components. The method preserves the extracellular matrix as a complex 3D biomimetic scaffold [3]. In an ideal scenario, cells would be harvested from the intended transplant recipient, then seeded into an ex vivo scaffold, grown in a bioreactor until the tissue reaches maturity, and finally transplanted to the patient [4]. In 2010, a research group paved the way for further research in this area, using the lung tissue engineering approach [5]. The authors treated the lungs of adult rats with a combination of chemicals that removes cellular components while preserving the extracellular matrix, which retains the hierarchical branching structures of airways and vasculature. Then, they used a bioreactor to culture a pulmonary epithelium and a vascular endothelium on the acellular lung matrix. The cultured epithelium displayed a great hierarchical organization, and the seeded endothelial cells were able to repopulate the vascular regions. The mechanical aspects of the engineered lungs assessed in vitro were similar to those of native lung tissue. The capability of basal gas exchange was also demonstrated [6].



Figure 1: The use of decellularized lung and repopulation with cells as an approach for lung tissue engineering [4].

The field of laryngeal tissue engineering, even though young, has progressed to the point where broad categories of research activity can be delineated and evaluated [7]. Ansari et al. (2017) decellularized porcine larynge, using detergents and enzymes to obtain scaffold comprising cartilage, muscle, and mucosa. The decellularized tissue seeded with human bone marrow‐derived mesenchymal stem cells and a tissue‐engineered oral mucosal sheet was implanted in pigs. The seeded grafts were left in situ for six months and assessed using computed tomography imaging, bronchoscopy, and mucosal brushings, with vocal recording and histological analysis on explanation. No adverse respiratory function or impact on the swallowing and the vocalization was caused by the graft, proposing a tissue engineering approach that represents a viable alternative treatment for laryngeal defects [8].



Figure 2: In vivo assessment of the implanted decellularized larynx. Adapted from [8].




REFERENCES

1. De Santis, M. M., Bölükbas, D. A., Lindstedt, S. & Wagner, D. E. How to build a lung: latest advances and emerging themes in lung bioengineering. Eur. Respir. J. 52, (2018).

2. Tebyanian, H. et al. Lung tissue engineering: An update. J. Cell. Physiol. 234, 19256–19270 (2019).

3. Stabler, C. T. et al. Revascularization of decellularized lung scaffolds: principles and progress. Am. J. Physiol. Lung Cell. Mol. Physiol. 309, L1273–85 (2015).

4. Gilpin, S. E. & Wagner, D. E. Acellular human lung scaffolds to model lung disease and tissue regeneration. Eur. Respir. Rev. 27, (2018).

5. Fishman, J. M., Lowdell, M. & Birchall, M. A. Stem cell-based organ replacements—Airway and lung tissue engineering. Semin. Pediatr. Surg. 23, 119–126 (2014).

6. Thibeault, S. L. & Welham, N. V. Strategies for advancing laryngeal tissue engineering. Laryngoscope 127, 2319–2320 (2017).

7. Ansari, T. et al. Stem Cell-Based Tissue-Engineered Laryngeal Replacement. Stem Cells Transl. Med. 6, 677–687 (2017).


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