Circumferential esophageal replacement using a tube-shaped tissue-engineered substitute: An experimental study in minipigs

22 September 2015

Esophageal replacement by the colon or the stomach for malignant and nonmalignant esophageal diseases exposes to significant morbidity and mortality. In this setting, tissue engineering
seems to be a seductive alternative.

Methods. In a porcine model, we performed a 5-cm-long circumferential replacement of the cervical
esophagus by a tubulized acellular matrix (small intestinal submucosa) cellularized with autologous
skeletal myoblasts and covered by a human amniotic membrane seeded with autologous oral epithelial
cells. The substitute was grown for 2 weeks in the great omentum before esophageal replacement. Eighteen minipigs (divided into 3 groups: group A [substitute with esophageal endoprothesis; n = 6], group B [substitute alone; n = 6], and group C [endoprothesis alone; n = 6]) were included.

The esophageal endoprothesis was removed at 6 months. Animals were killed sequentially over a 12 month-period.
Clinical, endoscopic, radiologic and histologic outcomes were analyzed.

Results. All animals except 1 of in groups B and C died during the first 2 months owing to refractory
esophageal stenosis or endoprothesis extrusion. Nutritional autonomy without endoprothesis was
observed in all animals of group A with a follow-up of >6 months (n = 3). A phenotype similar to that of
native esophagus, consisting of a mature epithelium, submucosal glands, and a circular muscular layer, was observed after 9 months.

Conclusion. In this model, the circumferential replacement of the cervical esophagus by a tube-shaped
tissue-engineered substitute under the temporary cover of an esophageal endoprothesis allowed
nutritional autonomy and tissue remodeling toward an esophageal phenotype. (Surgery 2015)

Tigran Poghosyan, MD, PhD,a,b,c Rony Sfeir, MD,d Laurent Michaud, MD,e
Patrick Bruneval, MD, PhD,f Thomas Domet, MSc,a Valerie Vanneaux, PharmD, PhD,a,c
Minh Luong-Nguyen, MD,a,c Sebastien Gaujoux, MD, PhD,g Frederic Gottrand, MD, PhD,e
Jerome Larghero, PharmD, PhD,a,c and Pierre Cattan, MD, PhD,a,b,c Paris and Lille, France



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