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

Author:

Rampino Teresa,Gregorini MarilenaORCID,Germinario GiulianaORCID,Pattonieri Eleonora Francesca,Erasmi Fulvia,Grignano Maria AntoniettaORCID,Bruno Stefano,Alomari Esra,Bettati StefanoORCID,Asti AnnaliaORCID,Ramus Marina,De Amici Mara,Testa Giorgia,Bruno StefaniaORCID,Ceccarelli GabrieleORCID,Serpieri Nicoletta,Libetta Carmelo,Sepe Vincenzo,Blasevich Flavia,Odaldi Federica,Maroni Lorenzo,Vasuri Francesco,La Manna Gaetano,Ravaioli MatteoORCID

Abstract

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.

Funder

National Health System Research

Publisher

MDPI AG

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology

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