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Pan-caspase inhibition during normothermic machine perfusion of discarded livers mitigates ischemia-reperfusion injury

ABSTRACT: Access to liver transplantation is limited by a significant organ shortage. The recent introduction of machine perfusion technology allows surgeons to monitor and assess ex situ liver function prior to transplantation. However, many donated organs are of inadequate quality for transplant, though opportunities exist to rehabilitate organ function with adjunct therapeutics during normothermic machine perfusion. In this preclinical study, we targeted the apoptosis pathway as a potential method of improving hepatocellular function. Treatment of discarded human livers during normothermic perfusion with an irreversible pan-caspase inhibitor, emricasan, resulted in significant mitigation of ischemia-reperfusion injury at both the transcriptional and protein level. This was evidenced by significantly decreased circulating levels of the pro-inflammatory cytokines, interleukin-6, interleukin-8, and interferon-gamma, compared to control livers. Untreated livers also demonstrated transcriptional changes notable for enrichment in pathways involved in innate immunity, leukocyte migration, and cytokine-mediated signaling. Targeting of unregulated apoptosis may represent a viable therapeutic intervention for rehabilitating liver hepatocellular function during machine perfusion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE202565 | GEO | 2022/07/11

REPOSITORIES: GEO

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

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Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers

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Pan-caspase inhibition during normothermic machine perfusion of discarded livers mitigates ischemia-reperfusion injury

Project description:Pan-caspase inhibition during normothermic machine perfusion of discarded livers mitigates ischemia-reperfusion injury

| PRJNA836578 | ENA

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Conditioning of porcine kidneys during dynamic preservation with exosomes derived from Urine Progenitor Cells

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