Development and qualification of clinical grade decellularized and cryopreserved human esophagi

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Godefroy, William | Faivre, Lionel | Sansac, Caroline | Thierry, Briac | Allain, Jean-Marc | Bruneval, Patrick | Agniel, Rémy | Kellouche, Sabrina | Monasson, Olivier | Peroni, Elisa | Setterblad, Niclas | Braik, Massymissa | Even, Benjamin | Cheverry, Sophie | Domet, Thomas | Albanese, Patricia | Larghero, Jérôme | Cattan, Pierre | Arakelian, Lousineh

Edité par CCSD ; Nature Publishing Group -

International audience. Tissue engineering is a promising alternative to current full thickness circumferential esophagealreplacement methods. The aim of our study was to develop a clinical grade Decellularized HumanEsophagus (DHE) for future clinical applications. After decontamination, human esophagi fromdeceased donors were placed in a bioreactor and decellularized with sodium dodecyl sulfate (SDS) andethylendiaminetetraacetic acid (EDTA) for 3 days. The esophagi were then rinsed in sterile water andSDS was eliminated by fltration on an activated charcoal cartridge for 3 days. DNA was removed bya 3-hour incubation with DNase. A cryopreservation protocol was evaluated at the end of the processto create a DHE cryobank. The decellularization was efcient as no cells and nuclei were observed inthe DHE. Sterility of the esophagi was obtained at the end of the process. The general structure of theDHE was preserved according to immunohistochemical and scanning electron microscopy images.SDS was efciently removed, confrmed by a colorimetric dosage, lack of cytotoxicity on Balb/3T3cells and mesenchymal stromal cell long term culture. Furthermore, DHE did not induce lymphocyteproliferation in-vitro. The cryopreservation protocol was safe and did not afect the tissue, preservingthe biomechanical properties of the DHE. Our decellularization protocol allowed to develop the frstclinical grade human decellularized and cryopreserved esophagus.

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