Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells

Saverio La Francesca,Robert D Odze,Kalia Burnette,Johnathon M Aho,Dennis A Wigle,Ellen W Blanco,Lena Kalenjian,Matthew Marsh,Matthew R Barron,Sherif Soliman,Ariel D Hanson,Elisaveta Todorova,Harout Dersimonian

doi:10.1038/s41598-018-22401-x

Saverio La Francesca, Robert D Odze + Show 11 more

Open Access

https://doi.org/10.1038/s41598-018-22401-x

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Abstract

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.

Highlights

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus
Within this work we describe an approach to in vivo esophageal regeneration using a temporary synthetic scaffold made of non-absorbable material that becomes separated from the esophagus and is retrieved, seeded with autologous adipose-derived mesenchymal stem cells (aMSCs), that when implanted supports esophageal regrowth in a large animal model of esophageal resection
The polyurethane scaffold and esophageal stent were removed 3 weeks later and after application of platelet rich plasma mixed with 15 million aMSC the esophageal stent was replaced

Summary

Introduction

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Reconstruction typically utilizes an alternative autologous tissue, either gastric, small bowel, or colon, as a conduit with removal of the esophagus distal to the diseased segment. These treatment modalities are associated with high morbidity and mortality[6,7,8,9]. There are significant challenges to the scalability of a clinically relevant tissue engineered construct generated in vitro, that are mostly related to the lack of ability, insofar, of creating large perfused scaffolds that allow for the diffusion of oxygen and nutrients and the disposal of waste products These challenges are especially arduous when the organ that needs to be regenerated has distinct spatial structural characteristics[14]

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