Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia

Albert C. Pai; Anthony M. Swatek; Thomas J. Lynch; Bethany A. Ahlers; Vitaly Ievlev; John F. Engelhardt; Kalpaj R. Parekh

doi:10.3390/bioengineering10070777

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Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia

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Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia

Albert C. Pai, Anthony M. Swatek, Thomas J. Lynch, Bethany A. Ahlers, Vitaly Ievlev, John F. Engelhardt and Kalpaj R. Parekh

Bioengineering (Basel), Vol.10(7), 777

06/29/2023

DOI: 10.3390/bioengineering10070777

PMCID: PMC10376427

PMID: 37508804

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Abstract

Tracheal grafts may be necessary to bridge long-segment defects after curative resection for airway obstructions. Bioengineered grafts have emerged as an appealing option, given the possibilities of altering the histologic and cellular profile of the conduit. We previously designed a bioreactor capable of luminally decellularizing and recellularizing a ferret trachea with surface airway epithelia (SAE) basal cells (BCs), and we sought to assess the fate of these grafts when transplanted in an orthotopic fashion. As adjuncts to the procedure, we investigated the use of a vascular endothelial growth factor (VEGF)-laden hydrogel and of immunosuppression (IS) in graft revascularization and viability. IS was shown to limit early graft revascularization, but this effect could be counteracted with VEGF supplementation. Submucosal gland (SMG) loss was shown to be inevitable regardless of the revascularization strategy. Lastly, the bioengineered tracheas survived one month after transplant with differentiation of our implanted BCs that then transitioned into a recipient-derived functional epithelium. The work presented in this manuscript has important implications for future cellular and regenerative therapies.

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Title: Subtitle: Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia
Creators: Albert C. Pai - University of Iowa
Anthony M. Swatek - University of Iowa
Thomas J. Lynch - University of Iowa
Bethany A. Ahlers - University of Iowa
Vitaly Ievlev - University of Iowa
John F. Engelhardt - University of Iowa
Kalpaj R. Parekh - University of Iowa
Resource Type: Journal article
Publication Details: Bioengineering (Basel), Vol.10(7), 777
DOI: 10.3390/bioengineering10070777
PMID: 37508804
PMCID: PMC10376427
NLM abbreviation: Bioengineering (Basel)
ISSN: 2306-5354
eISSN: 2306-5354
Grant note: DOI: 10.13039/100000050, name: NHLBI, award: R01 HL136370, K08 HL114725, 75N92019C00010, HL165404, HL152960, HL155843; name: NIDDK, award: P30 DK054759; name: Cystic Fibrosis Foundation; DOI: 10.13039/100010261, name: Thoracic Surgery Foundation for Research and Education, award: K105500-G
Language: English
Date published: 06/29/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
Record Identifier: 9984442031802771

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