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- Title
CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death.
- Authors
Grignano, Maria Antonietta; Bruno, Stefania; Viglio, Simona; Avanzini, Maria Antonietta; Tapparo, Marta; Ramus, Marina; Croce, Stefania; Valsecchi, Chiara; Pattonieri, Eleonora Francesca; Ceccarelli, Gabriele; Manzoni, Federica; Asti, Annalia; Libetta, Carmelo; Sepe, Vincenzo; Iadarola, Paolo; Gregorini, Marilena; Rampino, Teresa
- Abstract
We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.
- Subjects
STROMAL cells; EXTRACELLULAR vesicles; ANIMAL disease models; CELL death; ADENOSINE monophosphate; REPERFUSION injury
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 18, pN.PAG
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms231810681