Metabolite enhanced perfusion solution improves kidney transplantation viability
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PROVIDER: PRJNA1019717 | ENA |
REPOSITORIES: ENA
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Project description:Normothermic machine perfusion (NMP) has become a valuable tool to expand the pool of transplantable organs. However, the application of NMP to kidneys presents substantial challenges, mostly due to high variability in the configuration of perfusion buffers. Here we introduce a multimodal atlas of kidney cell injury associated with NMP using a literature-based consensus buffer. This resource provided the foundation for a systematic cross-species framework with integrated metabolic, genomic, spatial proteomic, and histopathologic profiling that was used to re-engineer the consensus perfusion buffer, mitigating cellular damage ex vivo and in vivo, thus extending organ viability and improving adequacy for transplantation.
2025-08-09 | GSE243729 | GEO
Project description:Background and Aims: Liver transplantation provides an effective cure for end-stage liver disease but is hampered by a severe organ shortage. Normothermic machine perfusion (NMP) of donor livers allows dynamic preservation in addition to viability assessment prior to transplantation. Little is known about the injury and repair mechanisms induced during NMP. Therefore, we examined gene and protein expression changes in a cohort of discarded human livers during NMP, stratified by liver viability. Approach and Results: 6 human livers from donation after circulatory death (DCD) underwent 12 hours of NMP, of which 3 met viability criteria. We applied bulk transcriptomics to evaluate differences in gene expression relating to injury, repair, and regenerative responses among livers based on viability. Viable livers demonstrated robust activation of innate immunity after 3 hours of NMP followed by enrichment of pro-repair and pro-survival mechanisms. Nonviable livers demonstrated delayed and persistent enrichment of innate immune responses. Viable livers demonstrated effective induction of autophagy, the cellular repair and homeostasis pathway, compared to nonviable livers. Enrichment of pro-survival signaling was also broader in these livers. Conclusions: NMP of discarded DCD human livers results in ischemia-reperfusion injury, but importantly activates autophagy as a means of cellular repair. More pronounced activation of autophagy was seen in livers that met viability criteria for transplantation. Therapeutic targeting of the autophagy mechanism may allow rehabilitation of nonviable livers for transplantation.
2022-01-25 | GSE165568 | GEO
Project description:Viability of discarded human livers during normothermic machine perfusion is associated with activation of repair mechanisms
| PRJNA694985 | ENA
Project description:We report the first use of ex vivo lung perfusion (EVLP) in the genetic and physiologic modification of lungs from deceased pulmonary arterial hypertension (PAH) patients and propose this as a translational platform to both (1) derive clinically relevant mechanistic insights into pulmonary pathophysiology and (2) to test treatments on human lungs. The EVLP consist in the perfusion of the lungs out of the body during 6 hours. It is a well established protocol in where basically lungs are on a table connected to a close circuit containing a special perfusion solution that is circulated through the pulmonary vein and artery using a pump. The circuit contains also a deoxygenator. The perfusion temperature and flow are adjusted gradually and after 20 mins of perfusion the ventilation is initiated. Every hour lungs are recruited in order to assess pulmonary function and collect perfusate samples. In addition to perfusate, tissue samples from the lower lobe of the left lung and bronchial alveolar lavage (BAL) are collected at times T0, 3 and 6 hr.
2015-06-02 | GSE69416 | GEO
Project description:Fermented Seed solution Raw sequence reads
| PRJNA1014181 | ENA
Project description:Background: Ex vivo oxygenated perfusion systems is a promising approach to extend cardiac allograft preservation beyond the typical 4–6h limit allowed by static-cold-storage (SCS). Hypothermic oxygenated perfusion (HOPE) has been proven to safely preserve donor hearts, yet its underlying molecular mechanisms have not been extensively evaluated. Objectives: The aim of the study is to characterize cardiomyocyte viability, transcriptomic and metabolomic responses, and functional recovery of porcine hearts preserved with HOPE for up to 48h, including evaluating their ability to regain sinus rhythm following bench-top normothermic reperfusion (NMP). Methods: Seventeen Yorkshire pigs underwent donor cardiectomy. In the first arm, ten hearts were preserved for up to 48h using either SCS (n=5) or HOPE (n=5). Endomyocardial biopsies were collected at 0, 12, 24, and 48h for histology, RNA sequencing, flow cytometry, and metabolomics. In the second arm, six HOPE-preserved hearts (3h, 24h, 48h) and two SCS-preserved heart (3h and 24h) underwent 2h NMP to simulate transplantation and assess reanimation. Results: HOPE preserved cardiomyocyte viability and structural integrity for 48h, in contrast to SCS in both arms of the study. RNA sequencing and untargeted metabolomics revealed conserved energy-substrate profiles in HOPE and progressive ischemic metabolite accumulation in SCS. All HOPE hearts regained stable sinus rhythm. Conclusions: HOPE enables 48h ex vivo heart preservation while maintaining cardiomyocyte integrity, normal gross and microscopic architecture, and rapid functional recovery on bench-top reperfusion in a preclinical model. These findings establish a foundation for redefining clinical preservation times and widening geographic donor access.
2025-12-24 | GSE314590 | GEO
Project description:This data was utilized to assess the utility of perfusion culture in cultivating spheroids of sarcoma cells. The differences between spheroids cultured with perfusion and without perfusion were analyzed through mass spectrometry. The spheroids were fabricated from NCC-UPS4-C1 cell line derived from a patient with undifferentiated pleomorphic sarcoma.
2024-02-02 | PXD049106 | JPOST Repository
Project description:We studies the effect of Akkermansia perfusion on human by taking biopsies before and after perfusion and assess gene expression. Affymetrix HuGene 1.1 ST arrays were used to assess whole biopsy gene expression profiles
2022-08-18 | GSE211506 | GEO