Department of Anesthesiology, Yale University, New Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
J Tissue Eng Regen Med. 2018 Mar;12(3):e1623-e1635. doi: 10.1002/term.2589. Epub 2017 Nov 28.
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.
开发供体肺的替代来源将改变肺移植的模式。最近的研究表明，使用脱细胞肺作为肺组织再生和随后植入的支架具有潜在的可行性。然而，寻找可靠的细胞来源并能够扩大肺支架的细胞再殖仍然是重大挑战。为了探索体外干细胞再生人肺组织的可能性，从人诱导多能干细胞 (iPSC) 中产生了肺祖细胞群体。为了探索从干细胞产生工程肺的可行性，我们用 iPSC 衍生的上皮祖细胞重新填充脱细胞的人肺和大鼠肺。在肺生物反应器系统中培养时，iPSC 衍生的上皮祖细胞排列在脱细胞的人肺上，并表达大多数上皮标志物。在脱细胞的大鼠肺中，这些人源细胞以类似于在脱细胞的人肺中观察到的方式附着和增殖。我们的结果表明，用 iPSC 衍生的肺上皮细胞重新填充肺基质可能是肺再生的可行策略，代表了向该技术转化的重要早期步骤。
