期刊
ADVANCED HEALTHCARE MATERIALS
卷 10, 期 21, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202100957
关键词
airway defects; biomaterials; bioreactors; in vivo; induced pluripotent stem cells; survival models; tissue engineering; trachea
资金
- Henry White Kinnear Fellowship
- University of Toronto Medicine by Design Initiative - Canada First Research Excellence Fund (CFREF) [C1TPA-2016-18]
Utilizing human induced pluripotent stem cells (hiPSCs) to engineer airway epithelial patches for transplantation has shown success in airway reconstruction, providing a significant advancement in this field.
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.
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