Open AccessHuman liver stem cell‐derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia
Author(s) -
De Stefano Nicola,
NavarroTableros Victor,
Roggio Dorotea,
Calleri Alberto,
Rigo Federica,
David Ezio,
Gambella Alessandro,
Bassino Daniela,
Amoroso Antonio,
Patrono Damiano,
Camussi Giovanni,
Romagnoli Renato
Publication year - 2021
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.13980
Subject(s) - medicine , ischemia , machine perfusion , perfusion , liver injury , andrology , extracellular , stem cell , liver transplantation , urology , pharmacology , pathology , transplantation , biology , biochemistry , microbiology and biotechnology
Summary Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell‐derived extracellular vesicles (HLSC‐EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC‐EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10 8 HLSC‐EVs/g‐liver, and (iv) warm ischemic livers treated with a 25 × 10 8 HLSC‐EVs/g‐liver. NMP lasted 6 h and HLSC‐EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC‐EV treatment significantly reduced transaminases release. Moreover, HLSC‐EVs enhanced liver metabolism by promoting phosphate utilization and pH self‐regulation. As compared to controls, the higher dose of HLSC‐EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC‐EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.