A5064762329- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Electrospun Nanofibers in Biomedical Applications
- Tissue Engineering and Regenerative Medicine
- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Transplantation: Methods and Outcomes
- Organ Donation and Transplantation
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Biochemical effects in animals
- Peptidase Inhibition and Analysis
- Graphene and Nanomaterials Applications
- Pregnancy and preeclampsia studies
- Cardiac Ischemia and Reperfusion
Massachusetts General Hospital
2014-2020
University Medical Center Groningen
2020
University of Groningen
2020
Shriners Hospitals for Children - Erie
2015-2020
Harvard University
2015-2019
VA Boston Healthcare System
2017
Creative Commons
2016
Shriners Hospitals for Children - Boston
2015-2016
Abstract The liver is a central organ in the human body and first line of defense between host external environment. Liver response to any perturbation collective reaction resident cells. Most current vitro models focus on hepatocytes, primary metabolic component, omitting interactions cues from surrounding environment non-parenchymal cells (NPCs). Recent studies suggest that contributions NPCs are vital, particularly disease conditions outcomes drugs their metabolites. Along with...
Abstract As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the liver. The transplantation donation after circulatory death (DCD) livers limited by poor outcomes, but its application may be expanded ex vivo repair and assessment before transplantation. Here we employed subnormothermic (21 °C) discarded human combined with metabolomics gain insight into metabolic recovery during perfusion. Improvements in energetic cofactors redox...
Whole liver engineering holds the promise to create transplantable grafts that may serve as substitutes for donor organs, addressing shortage in transplantation.While decellularization and recellularization of livers animal models have been successfully achieved, scale up human has slow.There are a number discarded because they not found suitable transplantation, but available grafts.These rejected due variety reasons, which turn affect outcome.Hence, one-size-fit-for all protocol result...
Ex situ machine perfusion is a promising technology to help improve organ viability prior transplantation. However, preclinical studies using discarded human livers evaluate therapeutic interventions and optimize conditions are limited by significant graft heterogeneity. In order the efficacy reproducibility of future studies, split-liver model was developed allow simultaneous left right lobes, allowing one lobe serve as control for other. Eleven were surgically split, both lobes perfused...
There continues to be a significant shortage of donor livers for transplantation. One impediment is the discard rate fatty, or steatotic, because their poor post-transplant function. Steatotic are prone ischemia-reperfusion injury (IRI) and data regarding how best improve quality steatotic lacking. Herein, we use normothermic (37°C) machine perfusion in combination with metabolic lipidomic profiling elucidate deficiencies pathways livers, inform strategies improving During perfusion, energy...
Steatosis is a major risk factor for primary nonfunction in liver transplantations. Steatotic livers recover poorly from ischemia reperfusion injury, part due to alterations the microcirculation, although exact mechanism unclear. In this study, we tested if there were any shear stress sensing Kruppel-like 2 (KLF2) and its likely downstream consequences ex vivo perfused human endothelium, which would imply perturbations microcirculatory flow macrosteatotic disrupts laminar evaluate potential...
Due to the growth of cell-based therapeutic alternatives addressing shortage livers for transplant, there is necessity a reliable source human hepatocytes. In addition, pharmaceutical research often requires hepatocytes assess new drug therapies during development or achieve FDA approval. Whole producing large quantities cells from same donor are ideal, enhancing reproducibility all purposes, while also allowing capturing variances in drug-metabolism across different demographics testing and...
Treatment for end-stage organ failure is restricted by the critical shortage of donor organs with waiting list currently at 100,000 requests and it increasing 5% every year. In case liver, about 4,000 people die in US while a transplantable organ, lack considered major health crisis. We previously demonstrated that ischemic whole rat livers can be decellularized to create an whole-liver scaffold, adult hepatocytes seeded into these scaffolds, recellularized auxiliary grafts transplanted...
BACKGROUND: The current gold standard in tissue preservation is static cold storage (SCS) on ice-cold (0–4°C) UW solution. While SCS slows down graft deterioration, it does not have restorative capabilities. We previously developed an ex-vivo perfusion system for subnomothermic oxygenated machine (SNMP) to resuscitate cadaveric organs. Recovered livers were perfused 3 hours and transplanted successfully into recipient rats 5/6 cases1; when scaled up DCD human livers, SNMP demonstrated...