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Author Spotlight: Modeling Human Airway Remodeling and Viral Responses Using Isogenic Epithelial, Endothelial, and Immune Cells
Published on: December 6, 2024
Short-Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial
Ratna Varma1,2, Alba E Marin-Araujo1, Sara Rostami1
1Latner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto General Hospital, University of Toronto, 101 College St, Toronto, ON, M5G 0A3, Canada.
Abstract:
Airway pathologies including cancer, trauma, and stenosis lack effective treatments, meanwhile airway transplantation and available tissue engineering approaches fail due to epithelial dysfunction. Autologous progenitors do not meet the clinical need for regeneration due to their insufficient expansion and differentiation, for which human induced pluripotent stem cells (hiPSCs) are promising alternatives. Airway epithelial patches are engineered by differentiating hiPSC-derived airway progenitors into physiological proportions of ciliated (73.9 ± 5.5%) and goblet (2.1 ± 1.4%) cells on a silk fibroin-collagen vitrigel membrane (SF-CVM) composite biomaterial for transplantation in porcine tracheal defects ex vivo and in vivo. Evaluation of ex vivo tracheal repair using hiPSC-derived SF-CVM patches demonstrate native-like tracheal epithelial metabolism and maintenance of mucociliary epithelium to day 3. In vivo studies demonstrate SF-CVM integration and maintenance of airway patency, showing 80.8 ± 3.6% graft coverage with an hiPSC-derived pseudostratified epithelium and 70.7 ± 2.3% coverage with viable cells, 3 days postoperatively. The utility of bioengineered, hiPSC-derived epithelial patches for airway repair is demonstrated in a short-term preclinical survival model, providing a significant leap for airway reconstruction approaches.
