Background and Aims The prevention/attenuation of graft ischemic injury is a challenge in kidney transplantation. We developed two rat models to investigate the impact of mesenchymal stromal cells (MSCs) in the ischemic preconditioning of kidneys from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD). Method Under general anesthesia, rats underwent iv injection of saline (S-groups) or 1.5 106 MSCs (MSC-groups) followed by either DBD (6hr of brain death) or DCD (6hr of anesthesia and 20min warm ischemia) models, resulting in 4 groups (S-DBD, S-DCD, MSC-DBD, MSC-DCD). Kidneys were then procured after IGL1 flush. One kidney was directly fixed and the other one immersed for 14 hours in IGL1 at 4°C. Serum samples were collected before treatment (baseline) and at the time of kidney collection. Urine samples were collected by bladder puncture at the time of kidney collection. Renal function was evaluated. Kidney histology was assessed by PAS staining and KIM1 immunostaining. Total RNA was extracted from S-DCD vs S-DBD kidneys for RNAseq. Results BUN was increased after 6h of anesthesia (DCD) or brain death (DBD) (p<0.01). SCr increased in both S-DBD and MSC-DBD but was lower in MSC-treated rats (MSC-DBD 0.5±0.2mg/dL vs S-DBD 0.7±0.1mg/dL; p = 0.037). Urinary KIM1 was lower in MSC-treated DBD (S-DBD 10.9±4.5 vs MSC-DBD 7.1±1.7; p = 0.03). Acute Tubular Injury (ATI) and KIM1 expression were higher in S-DBD (ATI: S-DBD 65±24% of surface vs S-DCD 39±27% of surface (p = 0.03) and KIM1: S-DBD 0.39±0.24% of surface vs S-DCD 0.10±0.09% of surface (p = 0.0002)). In MSC groups, there was no difference in both ATI extension and KIM1 expression. RNAseq showed that proinflammatory and proapoptotic pathways were upregulated in DBD, whereas transmembrane transport and metabolic pathways were downregulated, compared to DCD. Conclusion The RNA profiles of the kidneys are different upon donor types, which may impact the response to MSC-based ischemic preconditioning.
Enterotoxigenic Escherichia coli (ETEC) causing post-weaning diarrhea (PWD) in piglets have a detrimental impact on animal health and economy in pig production. ETEC strains can adhere to the host’s small intestinal epithelial cells using fimbriae such as F4 and F18. Phage therapy could represent an interesting alternative to antimicrobial resistance against ETEC infections. In this study, four bacteriophages, named vB_EcoS_ULIM2, vB_EcoM_ULIM3, vB_EcoM_ULIM8 and vB_EcoM_ULIM9, were isolated against an O8:F18 E. coli strain (A-I-210) and selected based on their host range. These phages were characterized in vitro, showing a lytic activity over a pH (4–10) and temperature (25–45 °C) range. According to genomic analysis, these bacteriophages belong to the Caudoviricetes class. No gene related to lysogeny was identified. The in vivo Galleria mellonella larvae model suggested the therapeutic potential of one selected phage, vB_EcoS_ULIM2, with a statistically significant increase in survival compared to non-treated larvae. To assess the effect of this phage on the piglet gut microbiota, vB_EcoS_ULIM2 was inoculated in a static model simulating the piglet intestinal microbial ecosystem for 72 h. This study shows that this phage replicates efficiently both in vitro and in vivo in a Galleria mellonella model and reveals the safety of the phage-based treatment on the piglet microbiota.
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