Expression data from biopsies of CIT study patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72355 | GEO | 2015/09/10
SECONDARY ACCESSION(S): PRJNA295241
REPOSITORIES: GEO
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Project description:We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features A retrospective, single-centered cohort study was designed to compare the safety and efficacy of rATG versus BAS for induction in patients who received a renal transplantation from a deceased donor between January 2007 and December 2012. Recipients with CIT greater than 20 hours were included in this study. Patients were excluded if they had received a prior transplantation or dual organ transplantation. Patients were followed for 12 months post-transplantation or until patient death, graft lost or lost to follow up. Patients in the rATG group received 1.5 mg per kilogram of body weight given intravenously with the initial dose given intraoperatively. Subsequent doses were given daily through post-operative day 3, for a total dose of 4.5-6.0 mg per kilogram. Dosing was adjusted based on daily white blood cell and platelet counts. BAS (20 mg given intravenously) was administered intraoperatively and the subsequent dose on day 3 post-transplantation. All patients received maintenance immunosuppression with tacrolimus, prednisone and mycophenolate mofetil. In total. 230 patients were transplanted with a CIT > 20 hours; 174 and 56 patients received rATG and BAS induction, respectively. Gene expression profiling ws carried out on a subset (n=28) of these patients' post transplant biopsies. Of those 28 patients, 16 received rATG and 12 received BAS induction treatment.
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Project description:Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
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Project description:Ischemia-reperfusion injury during liver transplantation is responsible for early allograft dysfunction (EAD) and failure, both of which are associated with a high risk of morbidity and mortality in the recipient. The purpose of this study was to study major transcriptional alterations in livers procured from different types of human liver donors in order to identify genetic profiles predictive of post-implantation function. We have analyzed samples form living donors (LD), donors after cardiac death (DCD), donors after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and donors after brain death without EAD (DBD). Two samples were obtained from each donor: sample A was taken immediately before cold perfusion (baseline) and sample B 2h after portal reperfusion. We identified clear differences in gene expression patterns according to donor source. Both samples A and B from DBD-EAD and DCD demonstrated over-expression of pro-apoptotic and inflammatory transcripts. However, in DBD and LD, expression of these genes was low at baseline and rose only after reperfusion. DBD and LD demonstrated the greatest increase in overall genetic expression after reperfusion when sample B was contrasted with A, indicating less baseline graft injury in these two groups. Grafts from LD were characterized by activation of transcripts related to anti-ischemic and regenerative processes and fewer pro-inflammatory gene transcripts. This transcriptional events occurring in liver allografts could allow for the prediction of post-transplant function. Pro-inflammatory and ischemic transcriptional changes in the grafts are directly related to donor type and may be useful targets for the development of future therapeutic strategies. The complete database comprised the expression for samples taken from 33 liver grafts. Sample A was taken immediately before cold perfusion (baseline) and sample B 2 h after portal reperfusion. Donors were from one of four groups: living (LD); after cardiac death (DCD); after brain death, with subsequent post-implantation EAD in the recipient (DBD-EAD); and after brain death without EAD (DBD). RNA was extracted from the 66 samples and analyzed using Illumina Beadarray technology. A group of 3 samples from healthy volunteers and 3 samples form LD taken at the start of surgery are included as controls or reference samples. This dataset is part of the TransQST collection.
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