Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors

Autor: Teresa Rampino, Marilena Gregorini, Giuliana Germinario, Eleonora Francesca Pattonieri, Fulvia Erasmi, Maria Antonietta Grignano, Stefano Bruno, Esra Alomari, Stefano Bettati, Annalia Asti, Marina Ramus, Mara De Amici, Giorgia Testa, Stefania Bruno, Gabriele Ceccarelli, Nicoletta Serpieri, Carmelo Libetta, Vincenzo Sepe, Flavia Blasevich, Federica Odaldi, Lorenzo Maroni, Francesco Vasuri, Gaetano La Manna, Matteo Ravaioli
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biology, Vol 11, Iss 3, p 350 (2022)
Druh dokumentu: article
ISSN: 2079-7737
DOI: 10.3390/biology11030350
Popis: The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.
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