Pre-Clinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Grafts
Pre-Clinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Grafts
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 grafts 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 grafts demonstrate native-like tracheal epithelial metabolism and maintenance of mucociliary epithelium to day 3. In vivo studies reveal SF-CVM integration, 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 post-operatively. We demonstrate the utility of bioengineered, hiPSC-derived epithelial grafts for airway repair in a pre-clinical survival model, providing a significant leap for airway reconstruction approaches.
Varma Ratna、Waddell Thomas K.、Karoubi Golnaz、Haykal Siba、Rostami Sara、Marin-Araujo Alba E.
Latner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College St||Institute of Biomedical Engineering, University of Toronto, 164 College StLatner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College St||Institute of Biomedical Engineering, University of Toronto, 164 College St||Institute of Medical Sciences, University of Toronto 27 King?ˉs College CirLatner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College St||Department of Mechanical and Industrial Engineering, University of Toronto, 5 King?ˉs College Circle||Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King?ˉs College CircleLatner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College St||Institute of Medical Sciences, University of Toronto 27 King?ˉs College Cir||Division of Plastic & Reconstructive Surgery, Department of Surgery, University of Toronto, 200 Elizabeth Street 8N-869Latner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College StLatner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, University Health Network, 101 College St
医学研究方法基础医学生物工程学
tracheabiomaterialstissue engineeringbioreactorsairway defectssurvival modeliPSC
Varma Ratna,Waddell Thomas K.,Karoubi Golnaz,Haykal Siba,Rostami Sara,Marin-Araujo Alba E..Pre-Clinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Grafts[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2021.05.18.444629.点此复制
评论