Abstract
Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their three-dimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes.
Highlights
Lung transplantation is the ultimate treatment option for end-stage lung diseases [1], such as chronic obstructive pulmonary disease, pulmonary fibrosis, and other refractory lung diseases
Our results clearly suggest that hPSC-derived lung progenitors (hLPs) expanded in microfibers can be useful for lung regeneration
To confirm the lung progenitor potency of microfiber-hLPs, we evaluated the differentiation of microfiber-hLPs into both alveolar and airway epithelial cells
Summary
Lung transplantation is the ultimate treatment option for end-stage lung diseases [1], such as chronic obstructive pulmonary disease, pulmonary fibrosis, and other refractory lung diseases. Endothelial progenitors, and adipose-derived stem cells have all been employed in cell-based therapies, such treatments were used for immunomodulatory and paracrine effects [4], and not for lung reconstruction. Lung epithelial stem cells are essential for lung regeneration [8], their obtention is challenging due to the difficulty of their expansion [9], and their potential for regenerative medicine purposes remains to be evaluated. Different methods for the induction of human pluripotent stem cell (hPSC)-derived lung progenitors (hLPs) and respiratory epithelial cells have been reported [10,11,12,13,14,15]. There have been reports of the transplantation of hPSC-derived cells into various human organs for therapeutic purposes [16,17]. The robust transplantation of hLPs into the alveoli, whose injury is tightly associated with the pathogenesis of various intractable lung diseases, has never been described
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
