Chronic liver disease and cirrhosis causes up 60,000 deaths annually in the US, over 4,000 of which are directly due to lack of a donor liver available for transplant. These numbers could be reduced dramatically should the donor organ pool be expanded by rendering marginal cases, such as Donors obtained after Cardiac Death (DCD), transplantable. It is estimated that about 6,000 cadaveric livers/yr are only marginally damaged by ischemia post-cardiac death and could be resuscitated for transplantation. There is evidence from our lab and others that machine perfusion is a very promising approach for recovering cadaveric organs that would be otherwise rejected from the donor pool. However, safe and effective clinical realization of such a machine perfusion device requires sophisticated algorithms that ensure tight control of the system, maximize the viability of the organ and accurately assess if the liver is ready for transplantation at the end of perfusion. There is a significant gap of methods and algorithms designed for assessing organ viability for transplantation in a quantitative and objective manner, which is a major bottleneck in clinical translation of marginal organ recovery technologies and vertical advancement of the field. Our long-term goal is to maximize the use of donor organs while ensuring the graft success upon transplant. The objective of the proposed study is to develop and test a dynamic, online method to assess liver transplant success in a small clinical study. The central hypothesis to be tested here is that the liver survival post-transplantation is correlated to its energy state and energy metabolism during machine perfusion. The work described here is expected to create a dynamic, on-line liver viability score which can be used to assess the condition of the donor organs prior to transplantation surgery, ultimately reducing the guesswork involved in transplantation and consequently increasing the use of marginal donor organs reducing deaths due to graft failure. This development is anticipated to increase the pace of clinical adoption of machine perfusion preservation studies for the liver, as well as other organs. The results of this work will also have a positive impact on engineering science by establishing the basis for integration of process design & control of these complex, dynamic organ preservation systems.
There is a crisis in donor organ availability: overall there about 120,000 patients on the UNOS organ waiting list, with the number increasing by about 5% annually. Chronic liver disease and cirrhosis causes up to 60,000 deaths annually in the US many of which perish on due to lack of a transplantable liver graft. One of the issues constraining efficient use of donor grafts is the lack of quantitative metrics to determine suitability for transplantation for donors that are less than ideal, which leads to discarding a large number of potentially viable grafts. This application proposes a clinical study to identify potential biomarkers of liver viability from graft biopsies, which would provide such an objective measure for use in quality determination.
| Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar et al. (2017) Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics. Metabolites 7: |
| Bruinsma, Bote G; Uygun, Korkut (2017) Subzero organ preservation: the dawn of a new ice age? Curr Opin Organ Transplant 22:281-286 |
| Bruinsma, Bote G; Avruch, James H; Sridharan, Gautham V et al. (2017) Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation. Transplantation 101:1637-1644 |
| Bruinsma, Bote G; Sridharan, Gautham V; Weeder, Pepijn D et al. (2016) Metabolic profiling during ex vivo machine perfusion of the human liver. Sci Rep 6:22415 |
| Bruinsma, Bote G; Avruch, James H; Weeder, Pepijn D et al. (2015) Functional human liver preservation and recovery by means of subnormothermic machine perfusion. J Vis Exp : |
| Bruinsma, Bote G; Berendsen, Tim A; Izamis, Maria-Louisa et al. (2015) Supercooling preservation and transplantation of the rat liver. Nat Protoc 10:484-94 |
| Puts, C F; Berendsen, T A; Bruinsma, B G et al. (2015) Polyethylene glycol protects primary hepatocytes during supercooling preservation. Cryobiology 71:125-9 |
| Izamis, Maria-Louisa; Perk, Sinem; Calhoun, Candice et al. (2015) Machine perfusion enhances hepatocyte isolation yields from ischemic livers. Cryobiology 71:244-55 |
| Bruinsma, Bote G; Wu, Wilson; Ozer, Sinan et al. (2015) Warm ischemic injury is reflected in the release of injury markers during cold preservation of the human liver. PLoS One 10:e0123421 |
| Bruinsma, B G; Yeh, H; Ozer, S et al. (2014) Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant 14:1400-9 |
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