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Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model
Conclusions. C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
Source: Transplantation - December 1, 2022 Category: Transplant Surgery Tags: Original Basic Science Source Type: research

Klotho Regulates Epithelial-to-Mesenchymal Transition In Vitro via Wnt/ β-Catenin Pathway and Attenuates Chronic Allograft Dysfunction in a Rat Renal Transplant Model
CONCLUSIONS Our results show that Klotho has a significant protective role against EMT, renal allograft fibrosis, and CAD following kidney transplantation, which is mediated by inhibition of the Wnt/ß-catenin signaling pathway.PMID:33737505 | DOI:10.12659/AOT.930066
Source: Annals of Transplantation - March 19, 2021 Category: Transplant Surgery Authors: Xiaojun Li Pei Lu Xue-Feng Shao Ting Jiang Feng Liu Gang Li Source Type: research

Review of Current Machine Perfusion Therapeutics for Organ Preservation
Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1–8°C) and normothermic settings. Here, we...
Source: Transplantation - August 26, 2020 Category: Transplant Surgery Tags: Reviews Source Type: research

Calcineurin Inhibitors Downregulate HNF-1β and May Affect the Outcome of HNF1B Patients After Renal Transplantation
Conclusions: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.
Source: Transplantation - August 24, 2016 Category: Transplant Surgery Tags: Original Clinical Science-General Source Type: research

Attenuating Ischemia-Reperfusion Injury in Kidney Transplantation by Perfusing Donor Organs With siRNA Cocktail Solution
Conclusions: In conclusion, this is the first demonstration that perfusing donor organs with an siRNA cocktail solution can induce gene silencing in the kidney and prevent kidneys from extended cold I/R injury in kidney transplantation, highlighting the promise of the clinical application of siRNA-based therapies in the preservation of donor organs.
Source: Transplantation - March 22, 2016 Category: Transplant Surgery Tags: Original Basic Science-General Source Type: research

BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP‐12
BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV‐specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)‐ and calcineurin‐inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR–SP6‐kinase activation. Sirolimus inhibition was rapid and effective up to 24�...
Source: American Journal of Transplantation - December 7, 2015 Category: Transplant Surgery Authors: H. H. Hirsch, K. Yakhontova, M. Lu, J. Manzetti Tags: Original Article Source Type: research

Inhibition of autophagy increases apoptosis during re‐warming after cold storage in renal tubular epithelial cells
In conclusion, autophagy inhibition in RTECs after CS/REW induces apoptotic cell death and may be deleterious as a therapy to decrease DGF. This article is protected by copyright. All rights reserved.
Source: Transplant International - September 30, 2014 Category: Transplant Surgery Authors: Swati Jain, Daniel Keys, Trevor Nydam, Robert J. Plenter, Charles L. Edelstein, Alkesh Jani Tags: Original Article Source Type: research

Cloning and expression of porcine β1,4 N‐acetylgalactosaminyl transferase encoding a new xenoreactive antigen
ConclusionThe functional isolation of the porcine B4GALNT2 gene from a PAEC expression library, the pattern of B4GALNT2 gene expression and its sensitization of HEK‐B4T cells to antibody binding and complement mediated lysis indicates that the enzymatic activity of porcine B4GALNT2 produces a new immunogenic non‐Gal glycan which contributes in part to the non‐Gal immune response detected after pig‐to‐baboon cardiac xenotransplantation.
Source: Xenotransplantation - September 1, 2014 Category: Transplant Surgery Authors: Guerard W. Byrne, Zeji Du, Paul Stalboerger, Heide Kogelberg, Christopher G. A. McGregor Tags: Original Article Source Type: research

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats
Abstract Prolonged hypothermic storage causes ischemia‐reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK‐2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK‐2 cellular structure, diminished cytoplasmic translocation of high‐mobility group box (HMGB) 1 and suppressed NF‐...
Source: American Journal of Transplantation - May 24, 2013 Category: Transplant Surgery Authors: H. Zhao, H. R. Watts, M. Chong, H. Huang, C. Tralau‐Stewart, P. H. Maxwell, M. Maze, A. J. T. George, D. Ma Tags: Original Article Source Type: research