Functional integration of an autologous engineered esophagus in a large-animal model

Durkin, Natalie; Hall, George T.; Lutman, Roberto; Scuglia, Marianna; Xenakis, Theodoros; Patera, Giulia; Di Biagio, Daniele; Yamada, Koji; Tullie, Lucinda; Scaglioni, Dominic; Shibuya, Soichi; Nikaki, Kornilia; Beesley, Max Arran; Saleh, Tarek; Garrido Flores, Matias; Borselle, Dominika; Karaluka, Valerija; Hutchinson, J. Ciaran; Khalaf, Sahira; Ogunbiyi, Olumide; Wu, Lei; Huang, Xia; Song, Wenhui; Loukogeorgakis, Stavros; Pellegata, Alessandro Filippo; Mantero, Sara; Cossu, Giulio; Li, Vivian S.W.; Borrelli, Osvaldo; Bonfanti, Paola; Castellano, Sergi; Gerli, Mattia Francesco Maria; McCann, Conor J.; Eaton, Simon; Pellegrini, Marco; De Coppi, Paolo

Functional integration of an autologous engineered esophagus in a large-animal model

Tools

Preview	PDF (Publisher's Version) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 19MB
	Other (Supplementary Information incl. Source Data) 21MB

Item Type:	Article
Title:	Functional integration of an autologous engineered esophagus in a large-animal model
Creators Name:	Durkin, Natalie, Hall, George T., Lutman, Roberto, Scuglia, Marianna, Xenakis, Theodoros, Patera, Giulia, Di Biagio, Daniele, Yamada, Koji, Tullie, Lucinda, Scaglioni, Dominic, Shibuya, Soichi, Nikaki, Kornilia, Beesley, Max Arran, Saleh, Tarek, Garrido Flores, Matias, Borselle, Dominika, Karaluka, Valerija, Hutchinson, J. Ciaran, Khalaf, Sahira, Ogunbiyi, Olumide, Wu, Lei, Huang, Xia, Song, Wenhui, Loukogeorgakis, Stavros, Pellegata, Alessandro Filippo, Mantero, Sara, Cossu, Giulio, Li, Vivian S.W., Borrelli, Osvaldo, Bonfanti, Paola, Castellano, Sergi, Gerli, Mattia Francesco Maria, McCann, Conor J., Eaton, Simon, Pellegrini, Marco and De Coppi, Paolo
Abstract:	Tissue engineering of the esophagus has been limited by stent dependance and poor muscle regeneration. Here we report an integrated strategy to engineer a 2.5-cm esophageal segment by microinjecting autologous pericyte-like myogenic precursors and fibroblasts in a decellularized porcine scaffold to repair circumferential defects in 10-kg minipigs (n = 8), modeling pediatric use. Bioreactor maturation induced a proangiogenic phenotype, with in vivo support from biodegradable intraluminal stents and a vascularizing pleural wrap. This coordinated approach yielded safe and effective esophageal conduits; oral feeding supported normal growth, morbidity resembled that of clinical esophageal replacement and was endoscopically manageable, and 63% (5/8) survived to the 6-month endpoint. Comprehensive multimodal analyses demonstrated progressive recapitulation of native architecture, with increasing neuromuscular regeneration and vascularization, correlating with functional recovery, absence of symptomatic stricture and the presence of secondary peristalsis by 6 months. These results demonstrate that the combination of complementary regenerative, conditioning and surgical strategies enables a functionally integrated, contractile esophageal graft with ongoing structural maturation without immunosuppression.
Keywords:	Animals, Mice, Pigs
Source:	Nature Biotechnology
ISSN:	1087-0156
Publisher:	Nature Publishing Group
Date:	20 March 2026
Official Publication:	https://doi.org/10.1038/s41587-026-03043-1
PubMed:	View item in PubMed
Related to:	URL URL Type https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE280737 External Dataset https://doi.org/10.5522/04/27303705 External Dataset https://github.com/george-hall-ucl/bioengineered_pig_esophagus_paper Software https://doi.org/10.5281/zenodo.18325700 Software

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year