Clinically adaptable size cartilage grafts generated from human embryonic stem cells enable tracheal repair in a porcine model
7 affiliations
- 1Department of Pediatric Surgery, Institute of Medicine, University of Tsukuba
- 2Center for Regenerative Medicine, National Center for Child Health and Development Research Institute
- 3Animal Medical Emergency Center, Tokyo University of Agriculture and Technology
- 4Division of Tissue Engineering, The University of Tokyo Hospital
- 5Kobayashi Regenerative Research Institute, LLC.
- 6National Cerebral and Cardiovascular Center Research Institute
- 7Department of Pediatric Surgery, International University of Health and Welfare School of Medicine
Abstract
Introduction Autologous costal cartilage grafting is commonly used for pediatric tracheal reconstruction; however, it has several limitations, including restricted availability and surgical invasiveness. In this study, we investigated the feasibility of a novel tracheal reconstruction approach using human embryonic stem cell–derived cartilage tissue (ESCaT). Methods ESCaT was differentiated from human embryonic stem cells (SEES2), and large-scale cartilage constructs were generated by integrating tissues derived from multiple culture dishes within a nylon mesh scaffold. Decellularized ESCaT (dESCaT) was subsequently produced using a high hydrostatic pressure method. These constructs were transplanted into a porcine tracheal defect model, and airway patency, histological changes, and immune responses were evaluated. In addition, similar analyses were performed in operational immunodeficient pigs (OIDPs) treated with immunosuppressive regimens. Results ESCaT was reproducibly generated as plate-shaped constructs with an average size of 18.2 × 14.2 × 4.4 mm, exhibiting sufficient mechanical strength to withstand suturing and airway pressure. In non-treated pigs, both ESCaT and dESCaT induced strong inflammatory responses after transplantation, resulting in loss or replacement of cartilage tissue. In contrast, in the OIDP model, dESCaT grafts were maintained, and airway patency ranged from 84.7% to 100.8%. Histological analysis revealed only mild inflammatory cell infiltration, along with evidence of epithelial regeneration. Conclusions ESCaT demonstrates clinically relevant size and mechanical strength, indicating its potential as a graft material for tracheal reconstruction. However, immune responses in xenogeneic transplantation remain a major challenge, and the combination of decellularization and immunomodulation is critical for graft survival. Further studies are required to reduce immunogenicity and optimize tissue maturation for future clinical applications.
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BibTeX
@article{tanaka2026clinically,
title = {{Clinically adaptable size cartilage grafts generated from human embryonic stem cells enable tracheal repair in a porcine model}},
author = {Nao Tanaka and JunLong Chen and Huai-Che Hsu and Arhans Chairul Ismael and Ren Itou and Lilika Tabata and Eiji Kobayashi and Tetsuji Yamaoka and Kouji Masumoto and Hidenori Akutsu and Makoto Komura and Shin Enosawa and Akihiro Umezawa and Yasushi Fuchimoto},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = jul,
doi = {10.1186/s13287-026-05195-y},
url = {https://doi.org/10.1186/s13287-026-05195-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Clinically adaptable size cartilage grafts generated from human embryonic stem cells enable tracheal repair in a porcine model
AU - Nao Tanaka
AU - JunLong Chen
AU - Huai-Che Hsu
AU - Arhans Chairul Ismael
AU - Ren Itou
AU - Lilika Tabata
AU - Eiji Kobayashi
AU - Tetsuji Yamaoka
AU - Kouji Masumoto
AU - Hidenori Akutsu
AU - Makoto Komura
AU - Shin Enosawa
AU - Akihiro Umezawa
AU - Yasushi Fuchimoto
PY - 2026
DA - 2026/07/01
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05195-y
UR - https://doi.org/10.1186/s13287-026-05195-y
AB - Introduction Autologous costal cartilage grafting is commonly used for pediatric tracheal reconstruction; however, it has several limitations, including restricted availability and surgical invasiveness. In this study, we investigated the feasibility of a novel tracheal reconstruction approach using human embryonic stem cell–derived cartilage tissue (ESCaT). Methods ESCaT was differentiated from human embryonic stem cells (SEES2), and large-scale cartilage constructs were generated by integrating tissues derived from multiple culture dishes within a nylon mesh scaffold. Decellularized ESCaT (dESCaT) was subsequently produced using a high hydrostatic pressure method. These constructs were transplanted into a porcine tracheal defect model, and airway patency, histological changes, and immune responses were evaluated. In addition, similar analyses were performed in operational immunodeficient pigs (OIDPs) treated with immunosuppressive regimens. Results ESCaT was reproducibly generated as plate-shaped constructs with an average size of 18.2 × 14.2 × 4.4 mm, exhibiting sufficient mechanical strength to withstand suturing and airway pressure. In non-treated pigs, both ESCaT and dESCaT induced strong inflammatory responses after transplantation, resulting in loss or replacement of cartilage tissue. In contrast, in the OIDP model, dESCaT grafts were maintained, and airway patency ranged from 84.7% to 100.8%. Histological analysis revealed only mild inflammatory cell infiltration, along with evidence of epithelial regeneration. Conclusions ESCaT demonstrates clinically relevant size and mechanical strength, indicating its potential as a graft material for tracheal reconstruction. However, immune responses in xenogeneic transplantation remain a major challenge, and the combination of decellularization and immunomodulation is critical for graft survival. Further studies are required to reduce immunogenicity and optimize tissue maturation for future clinical applications.
SN - 1757-6512
ER -