Liver Cryopreservation for Regenerative Medicine Applications

Abstract: The liver has unique regenerative properties that make it an ideal target for regenerative medicine applications. Hepatic systems are functional subunits of the liver and include hepatocytes, liver organoids, precision cut liver slices (PCLS), liver segments/lobes, and whole organs. Each has particular role in research, diagnostic, and therapeutic applications. In particular, hepatic systems have critical roles in pharmacotoxicology testing during drug discovery, liver pathophysiology research, and treatment of acute and chronic liver failure through bioartificial livers or liver transplant. However, each of these applications is limited by scarcity of donors and large variability between these donors. One strategy to mitigate these limitations would be to develop a method for cryopreserving hepatic systems. Cryopreservation could revolutionize how these tissues are used and ultimately save many lives. In this review, we will discuss the limitations for applying conventional methods of cryopreservation to hepatic systems and how new strategies for cryopreserving livers, PCLS, organoids, and hepatocytes by vitrification may overcome these limitations. Lay Summary: There is an ever-growing shortage of livers for transplant as well as for research and diagnostic applications. Strategies for liver cryopreservation, or storage at ultralow temperatures, could allow preservation of these organs and tissues indefinitely. Such methods for “banking” livers and liver tissues would revolutionize how they are used in research and the treatment of patients. Here we describe limitations of existing technology and propose a new strategy for indefinite storage of liver and liver tissues in a low-temperature vitrified, or glass-like, state.