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Merck

A defined road to tracheal reconstruction: laser structuring and cell support for rapid clinic translation.

Stem cell research & therapy (2022-07-17)
Alexey Fayzullin, Georgiy Vladimirov, Anastasia Kuryanova, Elvira Gafarova, Sergei Tkachev, Nastasia Kosheleva, Elena Istranova, Leonid Istranov, Yuri Efremov, Ivan Novikov, Polina Bikmulina, Kirill Puzakov, Pavel Petrov, Ivan Vyazankin, Andrey Nedorubov, Tatyana Khlebnikova, Valentina Kapustina, Pavel Trubnikov, Nikita Minaev, Aleksandr Kurkov, Valery Royuk, Vasily Mikhailov, Dmitriy Parshin, Anna Solovieva, Marina Lipina, Alexey Lychagin, Peter Timashev, Andrey Svistunov, Victor Fomin, Anastasia Shpichka
ABSTRACT

One of the severe complications occurring because of the patient's intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses-the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials.

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Sigma-Aldrich
Sodio cloruro, BioXtra, ≥99.5% (AT)
Supelco
Live/Dead Cell Double Staining Kit, suitable for fluorescence
Sigma-Aldrich
Ketoconazole, An inhibitor of cytochrome P-450 in steroid biosynthesis. An antifungal agent that displays potent anti-metastatic, anti-neoplastic, and anti-psoriatic activities.