Background: Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information.
View Article and Find Full Text PDFFor decades, transplantation has been a life-saving treatment for those fortunate enough to gain access. Nevertheless, many patients die waiting for an organ and countless more never make it onto the waitlist because of a shortage of donor organs. Concurrently, thousands of donated organs are declined for transplant each year because of concerns about poor outcomes post-transplant.
View Article and Find Full Text PDFVascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive.
View Article and Find Full Text PDFAfter cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges.
View Article and Find Full Text PDFMyocardial infarction (MI) produces acute changes in strain and stiffness within the infarct that can affect remote areas of the left ventricle (LV) and drive pathological remodeling. We hypothesized that intramyocardial delivery of a hydrogel within the MI region would lower wall stress and reduce adverse remodeling in Yorkshire pigs (n = 5). Tc-Tetrofosmin SPECT imaging defined the location and geometry of induced MI and border regions in pigs, and in vivo and ex vivo contrast cine computed tomography (cineCT) quantified deformations of the LV myocardium.
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