Donor lung tissues: Control vs. Primary graft dysfunction (PGD)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9102 | GEO | 2008/09/15
SECONDARY ACCESSION(S): PRJNA102629
REPOSITORIES: GEO
Similar Datasets
Project description:Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pre-transplant molecular markers for predicting PGD. To identify distinctive gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to the graft implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD. Matched factors used were: recipient age (± 10 years), recipient gender, recipient lung disease, and type of transplantation (single or bilateral). Keywords: Observational case-control study Matched case-control observational study: 10 primary graft dysfunction cases vs 16 Good outcome cases. One replicate per array.
2008-09-15 | E-GEOD-9102 | biostudies-arrayexpress
Project description:Expression profile of human donor lungs that have developed primary graft dysfunction (PGD) after lung transplantation and those that have not. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. Keywords: stress response
2007-06-06 | GSE8021 | GEO
Project description:BACKGROUND: Hypovolemia is common in lung donors before or after brain death. However, its impact on primary graft function (PGD) remains obscure. METHODS: A clinically relevant two-hit model of PGD was established by integrating hypovolemic shock (HS) and cold ischemia-reperfusion in a mouse model of orthotopic lung transplantation (LTx) from C57BL/6 to Balb/c. At -48 hours, HS was induced to donor by withdrawal of blood from femoral artery and keeping the mean arterial pressure at 15±5 mmHg for 4 h. At -24 hours, donor lungs were retrieved from mice with or without HS and stored at 0ºC until transplantation. CD11b-DTR mice were used as donor and treated with Diphtheria Toxin (DT) to deplete graft-infiltrating macrophages. RESULTS: HS mainly caused macrophage-predominant infiltration around pulmonary artery injury systemic inflammatory response, but little impairment of lung function even if in combination with cold ischemia-reperfusion. Transcriptional profiling showed HS pretreatment increased pulmonary damage and alveolar remodeling but ameliorated inflammatory infiltration when compared to one-hit model of 12 hours cold ischemia-reperfusion injury. The allografts with donor DT-treatment one day ahead of HS showed injury and dysfunction at donation and worsened further at 24 hours reperfusion, whereas the allografts with recipient DT-treatment immediately after transplantation showed similar function and histology to the control treated with saline. CONCLUSION: Donor hypovolemia causes pulmonary artery injury and infiltration but has little impact on allograft function, even in combination with 24 h cold ischemia. Graft-infiltrating macrophages are critical in protecting graft from HS-induced injury and cold ischemia-reperfusion injury.
2022-03-30 | GSE156322 | GEO
Project description:Background: Primary graft dysfunction (PGD) remains a challenge to lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for the rapid detection of PGD and the measurement of particle flow rate (PFR) from exhaled breath is a novel means to monitor disease. Methods: 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on the third post-operative day. Exhaled breath particles (EBPs) and PFR were measured on mechanical ventilation. EBPs were evaluated with mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Results: 9 recipients developed PGD and had significantly higher PFR (686.4 (449.7-8824.0) particles per minute (ppm)) compared to recipients without PGD (116.6 (79.7-307.4) ppm, p=0.0005). From proteomic analysis, porcine and human EBP proteins recapitulated the BAL and adherens and tight junction proteins were underexpressed in PGD tissue. Conclusions: Histological and proteomic analysis found significant changes to the alveolar-capillary barrier to explain the increased PFR in recipients with PGD. Combined with the similarity of proteomic profiles between EBPs and BALF, exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.
2024-04-05 | PXD046365 | Pride
Project description:Primary Graft Dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular non-classical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) are mobilized from the spleen and, upon entry into the allograft, permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that pharmacological or genetic depletion of donor NCM abrogated CM recruitment, single-cell RNAseq identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of human and murine tissues combined with murine knockouts and chimeras indicated that while IL1β was secreted by multiple cell lineages, donor NCM were responsible for the early activation of AM and CCL2 release. IL1β production by NCM was NLRP3 inflammasome-dependent and inhibited by donor treatment using a clinically approved sulphonylurea, Glyburide. Production of CCL2 in the donor AM occurred through IL1R-dependent activation of PKC and NFκB-pathway. Accordingly, we show that IL1β-dependent paracrine interaction between donor NCM and AM leads to recruitment of host AM necessary for PGD. Since depletion of donor NCM, IL1β or IL1R antagonism, and inflammasome inhibition, abrogated recruitment of CM as well as PGD and are feasible using FDA-approved compounds, our findings have potential for immediate clinical translation.
2024-02-01 | GSE166679 | GEO
Project description:Pre-existing lung restricted autoantibodies (LRA) are associated with a higher incidence of primary graft dysfunction (PGD) although it remains unclear whether LRA can drive its pathogenesis. In syngeneic murine left lung transplant recipients, pre-existing LRA worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor non-classical monocytes as well as host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecule was necessary for lung injury which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin proteins failed to rescue lung function. LRA- mediated injury was localized to the transplanted lung and dependent on IL1β-mediated permeabilization of pulmonary vascular endothelium which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL1R in the donor lungs prevented LRA-induced graft injury. In humans, pre-existing LRA was an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that pre-existing LRA can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.
2022-10-19 | GSE211501 | GEO
Project description:Donor lung tissues: Control vs. Primary graft dysfunction (PGD)
| PRJNA102629 | ENA
Project description:The study aims to evaluate the efficacy of liver transplantation in the context of non-resectable colorectal liver metastasis. The primary endpoint is the overall survival in this group of patients while the secondary endpoint is the disease-free survival.
Patients included in this protocol will be evaluated either for whole or partial liver transplantation from deceased or living donors.
Type of different transplantations proposed are as follows:
1. Whole liver graft or partial liver (split) from a deceased donor
2. Partial liver graft retrieved from a deceased donor and orthotopically implanted after having performed a left hepatectomy in the recipient.
3. Partial liver graft retrieved from a deceased donor and heterotopically implanted if total hepatectomy can not be performed.
4. Partial liver graft retrieved from a living donor and orthotopically implanted after having performed total hepatectomy.
5. Partial liver graft retrieved from a living donor and orthotopically implanted after having after having performed a left hepatectomy in the recipient.
6. Partial liver graft retrieved from a living donor and heterotopically implanted if total hepatectomy can not be performed.
In cases 2-3-5-6 total hepatectomy of native liver can be secondarily performed after having achieved a proper graft hypertrophy in order to avoid a small for size syndrome
| 2400483 | ecrin-mdr-crc
Project description:The frequency of delayed function of kidney transplants varies greatly and is associated with the quality of graft, donor age, and the duration of cold ischemia time. Body weight differences between donor and recipient can affect primary graft function. The underlying mechanism is poorly understood. Here, we have transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. 24 hours post-transplantation, serum creatinine level in H-WD recipients was significantly higher compared to that of L-WD recipients indicating impaired primary graft function. We detected a 10 fold higher transcription of IL-6 and dramatically increased tubular destruction in grafts from H-WD recipients. This was accompanied by decreased expression of genes associated with kidney function and an up-regulation of other genes such as cytochrome P450 isoforms, FosL and Trib3 as revealed by DNA microarray analysis. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and to cause tubular damage. Whereas, immediate neutralization of IL-6 receptor signaling rescued primary graft function resulting in low serum creatinine levels, well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function. The dataset comprises eight samples divided into four sample groups. Each group represents rat kidneys collected after allogeneic transplantation under a certain condition and includes two biological replicates. The first group is characterized by a high body weight difference between donor and recipient, rats in the second group exhibit a low weight difference. Group three and four are similar to group one, but underwent an additional treatment with anti-IL6R mAb or prednisolone immediately after transplantation.
2010-04-08 | E-GEOD-15813 | biostudies-arrayexpress
Project description:The field of graft preservation has made considerable strides in recent years improving outcomes related to solid organ restoration and regeneration. In lungs, the use of ex vivo lung perfusion (EVLP) in line with devices and treatments has shown promising results within preclinical and clinical studies with the potential to improve graft quality. The benefit of the therapy would be to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. Additionally, such therapies used in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post transplantation. The mechanism by which this treatment improves the donor lung on a molecular basis is not yet fully elucidated. We hypothesized that there were characteristic inflammatory and immunomodulatory differences between lungs treated with and without cytokine adsorption, reflecting in proteomic changes in gene ontology pathways and across inflammation-related proteins. In the current study we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts the lung function when used during EVLP and when used post transplantation as hemoperfusion in a porcine model. Lung tissue from EVLP and post lung transplantation were analyzed for their proteomic profile using mass spectrometry. The inflammatory and immune processes were compared between the treated and the non-treated groups to show the differences occurring between the forms of graft preservation.
2023-10-24 | PXD044413 | Pride