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Conditioning of porcine kidneys during dynamic preservation with exosomes derived from Urine Progenitor Cells

ABSTRACT: Backgroud: among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organ appears promising. We hypothesized that using a cell therapy based on exosomes derived from Urine Progenitor Cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR-related kidney damages. Methods: we isolated and characterized porcine UPCs and their exosomes (Exo). Then these were used in an ex vivo preclinical porcine kidney preservation model. Kidneys were subjected to warm ischemia (32min) then preserved by Hypothermic Machine Perfusion (HMP) for 24h before 5h of Normothermic Machine Perfusion (NMP). Three groups were performed (n=5-6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/Exo + NMP/vehicle, Group 3 (G3): HMP/Exo + NMP/Exo. Results: porcine UPCs were successfully isolated from urine and fully characterized as well as their exosomes which were found of expected size/phenotype. RNA-seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of Exo therapy. Conclusions: we showed the feasibility/efficacy of UPC-exosomes for hypothermic/normothermic kidney conditioning prior to transplantation, paving the way of combining machine perfusion with exosome-based cell therapy for organ conditioning.

ORGANISM(S): Sus scrofa

PROVIDER: GSE255005 | GEO | 2024/06/01

REPOSITORIES: GEO

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