Short-Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Patches

Ratna Varma^{1

2}, Alba E Marin-Araujo¹, Sara Rostami¹, Thomas K Waddell^{1

2

3}, Golnaz Karoubi^{1

4

5}, Siba Haykal^{1

3

6}

Affiliations

¹ Latner 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.
² Institute of Biomedical Engineering (BME), University of Toronto, 164 College St, Toronto, ON, M5S 3G9, Canada.
³ Institute of Medical Sciences, University of Toronto, 27 King's College Cir, Toronto, ON, M5S 1A8, Canada.
⁴ Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Circle, Toronto, ON, M5S 3G8, Canada.
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
⁶ Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, 200 Elizabeth Street 8N-869, Toronto, ON, M5G2P7, Canada.

PMID: 34569180
DOI: 10.1002/adhm.202100957

Short-Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Patches

Ratna Varma et al. Adv Healthc Mater. 2021 Nov.

. 2021 Nov;10(21):e2100957.

doi: 10.1002/adhm.202100957. Epub 2021 Sep 26.

Authors

Ratna Varma^{1

2}, Alba E Marin-Araujo¹, Sara Rostami¹, Thomas K Waddell^{1

2

3}, Golnaz Karoubi^{1

4

5}, Siba Haykal^{1

3

6}

Affiliations

¹ Latner 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.
² Institute of Biomedical Engineering (BME), University of Toronto, 164 College St, Toronto, ON, M5S 3G9, Canada.
³ Institute of Medical Sciences, University of Toronto, 27 King's College Cir, Toronto, ON, M5S 1A8, Canada.
⁴ Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Circle, Toronto, ON, M5S 3G8, Canada.
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
⁶ Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, 200 Elizabeth Street 8N-869, Toronto, ON, M5G2P7, Canada.

PMID: 34569180
DOI: 10.1002/adhm.202100957

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.

Keywords: airway defects; biomaterials; bioreactors; in vivo; induced pluripotent stem cells; survival models; tissue engineering; trachea.

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Short-Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Patches

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Short-Term Preclinical Application of Functional Human Induced Pluripotent Stem Cell-Derived Airway Epithelial Patches

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