Regeneration of tracheal neotissue in partially decellularized scaffolds

Abstract Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decell...

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Main Authors: Zheng Hong Tan, Sayali Dharmadhikari, Lumei Liu, Jane Yu, Kimberly M. Shontz, Jacob T. Stack, Christopher K. Breuer, Susan D. Reynolds, Tendy Chiang
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-023-00312-4
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author Zheng Hong Tan
Sayali Dharmadhikari
Lumei Liu
Jane Yu
Kimberly M. Shontz
Jacob T. Stack
Christopher K. Breuer
Susan D. Reynolds
Tendy Chiang
author_facet Zheng Hong Tan
Sayali Dharmadhikari
Lumei Liu
Jane Yu
Kimberly M. Shontz
Jacob T. Stack
Christopher K. Breuer
Susan D. Reynolds
Tendy Chiang
author_sort Zheng Hong Tan
collection DOAJ
description Abstract Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage. We previously demonstrated that PDTG support regeneration of host-derived neotissue. Here, we use a combination of microsurgical, immunofluorescent, and transcriptomic approaches to compare PDTG neotissue with the native airway and surgical controls. We report that PDTG neotissue is composed of native tracheal cell types and that the neoepithelium and microvasculature persisted for at least 6 months. Vascular perfusion of PDTG was established within 2 weeks and the graft recruited multipotential airway stem cells that exhibit normal proliferation and differentiation. Hence, PDTG neotissue recapitulates the structure and function of the host trachea and has the potential to regenerate.
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spelling doaj.art-c0db940d1af44a219fa5135946c3d2e32023-07-16T11:11:32ZengNature Portfolionpj Regenerative Medicine2057-39952023-07-018111110.1038/s41536-023-00312-4Regeneration of tracheal neotissue in partially decellularized scaffoldsZheng Hong Tan0Sayali Dharmadhikari1Lumei Liu2Jane Yu3Kimberly M. Shontz4Jacob T. Stack5Christopher K. Breuer6Susan D. Reynolds7Tendy Chiang8Center of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalCollege of Medicine, The Ohio State UniversityCenter of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Perinatal Research, Nationwide Children’s HospitalCenter of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalCenter for Perinatal Research, Nationwide Children’s HospitalCenter of Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children’s HospitalAbstract Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage. We previously demonstrated that PDTG support regeneration of host-derived neotissue. Here, we use a combination of microsurgical, immunofluorescent, and transcriptomic approaches to compare PDTG neotissue with the native airway and surgical controls. We report that PDTG neotissue is composed of native tracheal cell types and that the neoepithelium and microvasculature persisted for at least 6 months. Vascular perfusion of PDTG was established within 2 weeks and the graft recruited multipotential airway stem cells that exhibit normal proliferation and differentiation. Hence, PDTG neotissue recapitulates the structure and function of the host trachea and has the potential to regenerate.https://doi.org/10.1038/s41536-023-00312-4
spellingShingle Zheng Hong Tan
Sayali Dharmadhikari
Lumei Liu
Jane Yu
Kimberly M. Shontz
Jacob T. Stack
Christopher K. Breuer
Susan D. Reynolds
Tendy Chiang
Regeneration of tracheal neotissue in partially decellularized scaffolds
npj Regenerative Medicine
title Regeneration of tracheal neotissue in partially decellularized scaffolds
title_full Regeneration of tracheal neotissue in partially decellularized scaffolds
title_fullStr Regeneration of tracheal neotissue in partially decellularized scaffolds
title_full_unstemmed Regeneration of tracheal neotissue in partially decellularized scaffolds
title_short Regeneration of tracheal neotissue in partially decellularized scaffolds
title_sort regeneration of tracheal neotissue in partially decellularized scaffolds
url https://doi.org/10.1038/s41536-023-00312-4
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