Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

Edward Hannon; Marco Pellegrini; Federico Scottoni; Natalie Durkin; Soichi Shibuya; Roberto Lutman; Toby J Proctor; J Ciaran Hutchinson; Owen J Arthurs; Demetra-Ellie Phylactopoulos; Elizabeth F Maughan; Colin R Butler; Simon Eaton; Mark W Lowdell; Paola Bonfanti; Luca Urbani; Paolo De Coppi

doi:10.1016/j.isci.2022.105174

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

iScience. 2022 Sep 22;25(10):105174. doi: 10.1016/j.isci.2022.105174. eCollection 2022 Oct 21.

Authors

Edward Hannon^{1

2}, Marco Pellegrini¹, Federico Scottoni^{1

3}, Natalie Durkin¹, Soichi Shibuya¹, Roberto Lutman¹, Toby J Proctor⁴, J Ciaran Hutchinson^{1

5}, Owen J Arthurs^{1

6}, Demetra-Ellie Phylactopoulos^{1

7}, Elizabeth F Maughan^{1

8}, Colin R Butler^{1

9}, Simon Eaton¹, Mark W Lowdell⁴, Paola Bonfanti^{1

7

10}, Luca Urbani^{11

12}, Paolo De Coppi^{1

13}

Affiliations

¹ Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
² Department of Paediatric Surgery, Leeds Children's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK.
³ Department of Pediatric Surgery, Regina Margherita Children's Hospital, Turin 10126, Italy.
⁴ Centre for Cell, Gene and Tissue Therapies, Royal Free Hospital & University College London, London NW3 2PF, UK.
⁵ Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
⁶ Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
⁷ Epithelial Stem Cell Biology & Regenerative Medicine Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
⁸ Charing Cross Airway Service, Department of Otolaryngology, Charing Cross Hospital, Imperial Healthcare NHS Trust, London W6 8RF, UK.
⁹ ENT Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
¹⁰ Institute of Immunity & Transplantation, University College London, London NW3 2PP, UK.
¹¹ The Roger Williams Institute of Hepatology, Foundation for Liver Research, London SE5 9NT, UK.
¹² Faculty of Life Sciences and Medicine, King's College London, London SE5 8AF, UK.
¹³ Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

Abstract

Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model.

Keywords: Biological sciences; Biomedical engineering; Biotechnology; Tissue engineering.

Grants and funding

MR/R002118/1/MRC_/Medical Research Council/United Kingdom