BACKGROUND: Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function. METHODS: We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. Liver allografts underwent HMP for 4-7 h using dual centrifugal perfusion with Vasosol solution at 4-8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism. RESULTS: We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP. CONCLUSIONS: HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.
BACKGROUND: Hypothermic machine perfusion (HMP) has shown significant benefits in renal transplantation but is still in its infancy in liver transplantation. Potential benefits include diminished preservation injury and improved early graft function. METHODS: We analyzed liver tissue and effluent collected during our Phase 1 trial of liver HMP. Liver allografts underwent HMP for 4-7 h using dual centrifugal perfusion with Vasosol solution at 4-8°C were transplanted and compared with cold stored (CS) transplant controls. Histology, reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry on liver biopsies compared histology and expression of early proinflammatory cytokines, IL-8 and TNF-α, and intracellular adhesion molecule-1 (ICAM-1). Gel electrophoresis was used to evaluate effluent protein content representing residual metabolism. RESULTS: We saw no differences between HMP and CS in early histologic findings after reperfusion. RT-PCR of reperfusion biopsy samples in the CS group showed high expression of proinflammatory cytokines and ICAM-1. This up-regulation was significantly attenuated by HMP (ICAM-1; P = 0.0152) (IL-8; P = 0.0014) (TNF-α; P = 0.0284). This was confirmed with immunohistochemistry. Albumin was identified in the perfusate throughout HMP. CONCLUSIONS: HMP significantly reduced proinflammatory cytokine expression compared with CS controls. Further studies of human liver HMP with detailed molecular investigations are now warranted to elucidate benefits of HMP in liver transplantation.
Authors: Maria-Louisa Izamis; Candice Calhoun; Basak E Uygun; Maria Angela Guzzardi; Gavrielle Price; Martha Luitje; Nima Saeidi; Martin L Yarmush; Korkut Uygun Journal: Cell Med Date: 2013
Authors: Nir I Nativ; Alvin I Chen; Gabriel Yarmush; Scot D Henry; Jay H Lefkowitch; Kenneth M Klein; Timothy J Maguire; Rene Schloss; James V Guarrera; Francois Berthiaume; Martin L Yarmush Journal: Liver Transpl Date: 2013-12-12 Impact factor: 5.799
Authors: N I Nativ; T J Maguire; G Yarmush; D L Brasaemle; S D Henry; J V Guarrera; F Berthiaume; M L Yarmush Journal: Am J Transplant Date: 2012-10-11 Impact factor: 8.086
Authors: Herman Tolboom; Maria-Louisa Izamis; Nripen Sharma; Jack M Milwid; Basak Uygun; François Berthiaume; Korkut Uygun; Martin L Yarmush Journal: J Surg Res Date: 2011-03-29 Impact factor: 2.192
Authors: Hieu Le Dinh; Arnaud de Roover; Abdour Kaba; Séverine Lauwick; Jean Joris; Jean Delwaide; Pierre Honoré; Michel Meurisse; Olivier Detry Journal: World J Gastroenterol Date: 2012-09-07 Impact factor: 5.742
Authors: Nir I Nativ; Gabriel Yarmush; Alvin Chen; David Dong; Scot D Henry; James V Guarrera; Kenneth M Klein; Tim Maguire; Rene Schloss; Francois Berthiaume; Martin L Yarmush Journal: J Hepatol Date: 2013-07-19 Impact factor: 25.083