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| Item Type: | Article |
|---|---|
| Title: | Functional integration of an autologous engineered esophagus in a large-animal model |
| Creators: |
Durkin, Natalie, Hall, George T.  ORCID: https://orcid.org/0000-0002-4828-0668, Lutman, Roberto, Scuglia, Marianna, Xenakis, Theodoros ORCID: https://orcid.org/0000-0003-3682-8873, Patera, Giulia, Di Biagio, Daniele, Yamada, Koji ORCID: https://orcid.org/0009-0003-9701-3018, Tullie, Lucinda, Scaglioni, Dominic ORCID: https://orcid.org/0000-0002-0441-2198, Shibuya, Soichi ORCID: https://orcid.org/0000-0002-4274-1312, Nikaki, Kornilia ORCID: https://orcid.org/0000-0002-8968-8926, Beesley, Max Arran, Saleh, Tarek, Garrido Flores, Matias, Borselle, Dominika ORCID: https://orcid.org/0000-0002-4880-8047, Karaluka, Valerija, Hutchinson, J. Ciaran ORCID: https://orcid.org/0000-0002-1708-2634, Khalaf, Sahira, Ogunbiyi, Olumide, Wu, Lei ORCID: https://orcid.org/0000-0002-0268-6304, Huang, Xia, Song, Wenhui ORCID: https://orcid.org/0000-0001-8406-472X, Loukogeorgakis, Stavros, Pellegata, Alessandro Filippo, Mantero, Sara ORCID: https://orcid.org/0000-0002-1264-0465, Cossu, Giulio ORCID: https://orcid.org/0000-0001-5863-9593, Li, Vivian S.W. ORCID: https://orcid.org/0000-0003-2041-0085, Borrelli, Osvaldo ORCID: https://orcid.org/0000-0003-0241-0508, Bonfanti, Paola ORCID: https://orcid.org/0000-0001-9655-3766, Castellano, Sergi, Gerli, Mattia Francesco Maria ORCID: https://orcid.org/0000-0002-9331-7394, McCann, Conor J. ORCID: https://orcid.org/0000-0002-9324-5984, Eaton, Simon ORCID: https://orcid.org/0000-0003-0892-9204, Pellegrini, Marco ORCID: https://orcid.org/0000-0002-3724-6640 and De Coppi, Paolo ORCID: https://orcid.org/0000-0002-1659-0207
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| 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: |
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