TOPLINE:

In a minipig model, implantation of autologous tissue‑engineered esophageal grafts supported 100% 30-day survival, restored oral feeding and normal growth, and demonstrated functional recovery, all without the need for immunosuppression. Early complications were managed endoscopically, and a majority of animals survived even at 6 months.

METHODOLOGY:

• In infants with long-gap esophageal atresia, current treatment options are often inadequate, prompting tissue engineering approaches to develop personalized circumferential grafts without damaging existing organs.
• Researchers performed a single-arm pilot study in eight female minipigs (initially 8 weeks old; weight, 4-5 kg) to evaluate the feasibility and safety of autologous tissue-engineered esophageal grafts for repairing 2.5-cm thoracic esophageal defects, modeling pediatric use.
• They prepared a tube-shaped scaffold from a donor pig esophagus by removing donor cells while preserving the structural matrix, seeded it with each minipig’s own expanded muscle precursor and fibroblast cells from a small biopsy; the seeded grafts were matured in a bioreactor for 1 week. The full manufacturing process took about 8 weeks.
• The engineered esophageal segments were implanted through thoracotomy, with biodegradable intraluminal stents and a vascularizing pleural wrap for support; animals received oral water immediately and progressed to full oral feeding from postoperative day 1 without supplemental nutrition.
• The primary outcome was survival at 6 months; secondary outcomes included 30-day mortality, maintenance of oral feeding and growth, functional motility, graft healing and integration over time, and morbidity related to perioperative and endoscopic interventions.

TAKEAWAY:

• All eight (100%) minipigs survived the first 30 days; five (63%) reached the planned 6-month follow-up point and were asymptomatic, tolerated oral feeds, and showed normal growth trajectories; four of the five animals did not require endoscopic interventions after 3 months.
• At 3 and 6 months, diagnostic tests measuring the pressure and motility of the esophagus showed that delivering a liquid bolus into the throat triggered wave‑like muscle contractions through the grafts, lasting about 7.2 seconds on average; this response was confirmed in five of seven animals, suggesting that the grafts can support swallow‑like movements.
• The implanted grafts demonstrated progressive recapitulation of native esophageal architecture over time, with the 6-month grafting exhibiting more organized tissue layers (epithelium, muscularis mucosa, submucosa, and muscularis externa) resembling a healthy esophagus.
• Adverse events included frequent stent migration leading to strictures requiring repeated endoscopic balloon dilations and stent replacements; early hyperplastic epithelial polyps were observed in all animals and were treated with steroids or endoscopic resection; no anastomotic leaks, pneumothorax, or infections were observed.

IN PRACTICE:

“Graft implantation was safe and effective, supporting oral feeding, maintaining structural integrity, and facilitating animal growth and survival,” the authors of the study wrote.

“Graft production was achieved in 8 weeks, well within the typical clinical timeframe for esophageal reconstruction in infants with LGEA [long-gap esophageal atresia], supporting translational feasibility,” they added.

SOURCE:

The study was led by Natalie Durkin, Stem Cell and Regenerative Medicine Section, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health in London, England. It was published online in Nature Biotechnology.

LIMITATIONS:

The study used shorter grafts (2.5 cm) tailored for pediatric long‑gap esophageal atresia, which may not directly translate to adult applications requiring longer grafts for conditions such as caustic injury or carcinoma. The seeded cells were unlabeled, preventing tracking of cell persistence within the grafts.

DISCLOSURES:

This work was supported by the National Institute for Health and Care Research Great Ormond Street Hospital (GOSH) Biomedical Research Centre, GOSH Charity, the LifeArc Translational Research Accelerator, and a Rosetrees Trust Major Project Award. Individual authors received additional support. One author declared being a named inventor on two patents.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.