Bioengineered lungs generated from human i PSC s‐derived epithelial cells on native extracellular matrix

Abstract

The development of an alternative source for donor lungs would change the paradigm of lung transplantation. Recent studies have demonstrated the potential feasibility of using decellularized lungs as scaffolds for lung tissue regeneration and subsequent implantation. However, finding a reliable cell source and the ability to scale up for recellularization of the lung scaffold still remain significant challenges. To explore the possibility of regeneration of human lung tissue from stem cells in vitro, populations of lung progenitor cells were generated from human iPSCs. To explore the feasibility of producing engineered lungs from stem cells, we repopulated decellularized human lung and rat lungs with iPSC-derived epithelial progenitor cells. The iPSCs-derived epithelial progenitor cells lined the decellularized human lung and expressed most of the epithelial markers when were cultured in a lung bioreactor system. In decellularized rat lungs, these human-derived cells attach and proliferate in a manner similar to what was observed in the decellularized human lung. Our results suggest that repopulation of lung matrix with iPSC-derived lung epithelial cells may be a viable strategy for human lung regeneration and represents an important early step toward translation of this technology.

Strategies based on organ decellularization and recellularization

“…Here, induced pluripotent stem cell-derived cells are favoured because of their expansion potential and autologous origin [16,76,103,105,108]. For recellularization, iPSCderived pulmonary cells are favoured because of their expansion potential and autologous origin [76,109].…”

Viral pandemic preparedness: A pluripotent stem cell-based machine-learning platform for simulating SARS-CoV-2 infection to enable drug discovery and repurposing

“…The genomic and phenotypic profiles of uninfected wild-type aiLUNG (aiLUNG-WT) cells and aiLUNG-COVID19 simulations were validated based on the currently available experimental wet lab and other data. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Ideally, in the future, this new technology would be implemented as soon as the new viral genome has been identified and validated. For example, the SARS-CoV-2 genome and cell receptor data were published in early March 2020 (GenBank accession number: MT126808.1).…”

Lung Microvascular Niche, Repair, and Engineering

“…In order to reduce ECM damage during the decellularization procedure, researchers have improved their protocols including the detergents used for decellularization ( Table 1). For the rat lung decellularization, Niklason's group first used zwitterionic detergents such as 8 mM 3-[(3-cholamidopropyl) dimethylammonio]-1-pro-panesulfonate (CHAPS) solution and then moved to stepwise concentrations of ionic/non-ionic detergent sodium deoxycholate (SDC)/Triton X-100 (Petersen et al, 2010;Calle et al, 2016;Ghaedi et al, 2018). Ott's group has used the denaturing anionic detergent 0.1% sodium dodecyl sulfate (SDS)/0.1% Triton X-100 (Ott et al, 2010;Gilpin et al, 2014Gilpin et al, , 2017.…”