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Metabolite enhanced perfusion solution improves kidney transplantation viability

ABSTRACT: Metabolite enhanced perfusion solution improves kidney transplantation viability

PROVIDER: PRJNA1019717 | ENA |

REPOSITORIES: ENA

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Metabolite enhanced perfusion solution improves kidney transplantation viability

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

Viability of discarded human livers during normothermic machine perfusion is associated with activation of repair mechanisms

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

Viability of discarded human livers during normothermic machine perfusion is associated with activation of repair mechanisms

Project description:Viability of discarded human livers during normothermic machine perfusion is associated with activation of repair mechanisms

| PRJNA694985 | ENA

Human ex vivo Lung Perfusion: A Pre-Clinical Model for Lung Disease

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

Bacteria solution

Project description:Bacteria solution Raw sequence reads

| PRJNA1278922 | ENA

Bacteria solution 1

Project description:Bacteria solution 1 Raw sequence reads

| PRJNA1272312 | ENA

Fermented Seed solution

Project description:Fermented Seed solution Raw sequence reads

| PRJNA1014181 | ENA

Gene expression data from Akkermansia perfusion trial

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

Comparison between sarcoma spheroids cultured with perfusion and without perfusion.

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

Newly synthesized glycoproteins during ex vivo lung perfusion

Project description:Proteins that were newly-synthesized during ex vivo lung perfusion were labeled with an azido-sugar Ac4GalNAz in the perfusate. These proteins were enriched using click chemistry to attach an alkyne-desthiobiotin group to the azido-labeled proteins, then pulled out of solution using streptavidin beads. The overall goal is to better understand the effects of warm ischemia injury in lungs destined for lung transplantation.

2022-10-07 | MSV000090491 | MassIVE

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