J Tissue Eng Regen Med. 2019 Oct 31. doi: 10.1002/term.2983. [Epub ahead of print]

A clinical-grade acellular matrix for esophageal replacement.

Arakelian L^1,2, Caille C^1,2, Faivre L^1,2, Corté L^3,4, Bruneval P⁵, Shamdani S⁶, Flageollet C⁶, Albanese P⁶, Domet T^1,2, Jarraya M⁷, Setterblad N⁸, Kellouche S⁹, Larghero J^1,2, Cattan P^2,10, Vanneaux V^1,2.

Abstract

In pathologies of the esophagus such as esophageal atresia, cancers and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix. Following the decontamination step, porcine esophagi were decellularized in a bioreactor with SDS and EDTA for three days and were rinsed with deionized water. DNA was eliminated by a three hour DNase treatment. To remove any residual detergent, the matrix was then incubated with an absorbing resin. The resulting porcine esophageal matrix was characterized by the assessment of the efficiency of the decellularization process (DNA quantification), evaluation of sterility and absence of cytotoxicity, its composition and biomechanical properties, as well as the possibility to be reseeded with mesenchymal stem cells. Complete decellularization with the preservation of the general structure, composition and biomechanical properties of the native esophageal matrix was obtained. Sterility was maintained throughout the process and the matrix showed no cytotoxicity. The resulting matrix met clinical grade criteria and was successfully reseeded with MSCs.