Abstract
Whole-organ decellularization technology has emerged as a new alternative for the fabrication of bioartificial lungs. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can be directed to express phenotypic marker genes of lung epithelial cells, being a potential cell source for recellularization of acellular lung scaffolds. Normal pulmonary development takes place in a relative hypoxic environment, but in vitro ES/iPS differentiation protocols are usually carried out at room-air oxygen tension. Here, we sought to determine the role played by oxygen tension on the derivation of Foxa2+Nkx2.1+ lung progenitor cells from mouse ESC and iPSC. A step-wise differentiation protocol was used to generate Foxa2+Nkx2.1+ lung progenitors at 20% and 5% oxygen tension. On day 12, gene expression analysis revealed that Nkx2.1 was significantly up-regulated at 5% oxygen tension in ESC and iPSC differentiated cultures compared to 20% oxygen conditions. In addition, quantification of Foxa2+Nkx2.1+Pax8- cells corresponding to the lung field, with exclusion of the potential fate identified by Pax8 expression, confirmed that low oxygen tension exerted a significant positive effect on early pulmonary differentiation of ES and iPS cells. In conclusion, we found that 5% oxygen tension enhanced the derivation of lung progenitors from mouse ESC and iPSC compared to 20% room-air oxygen tension, suggesting that an oxygen partial pressure similar to the physiological one at tissue level could optimize organ regeneration in lung bioengineering.
Supported in part by the Spanish Ministry of Economy and Competitiviness (SAF2011-22576).
- © 2014 ERS
