Long-Term Stability of Cryopreserved Human Hepatocytes: Evaluation of Phase I and II Drug-Metabolizing Enzyme Activities and CYP3A4/5 Induction for More than a Decade

• Published in: Drug metabolism and disposition Vol. 45; no. 7; pp. 734 - 736
• Main Authors: Sudo, Miyako, Nishihara, Mitsuhiro, Takahashi, Junzo, Asahi, Satoru
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics, Inc 01.07.2017
• Subjects: Aged; Aged, 80 and over; Cryopreservation; Cryopreservation - methods; CYP1A2 protein; Cytochrome; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 CYP3A - metabolism; Cytochrome P450; Drug metabolism; Enzymatic activity; Enzyme Induction - physiology; Female; Glucuronosyltransferase - metabolism; Hepatocytes; Hepatocytes - metabolism; Humans; Liquid nitrogen; Liver - metabolism; Male; Metabolic Clearance Rate - physiology; Metabolic Detoxication, Phase I - physiology; Metabolic Detoxication, Phase II - physiology; Metabolism; Qualitative research; Stability analysis; Storage; Sulfotransferase; Sulfotransferases - metabolism; Uridine; Vapor phases; Viability
• ISSN: 0090-9556; 1521-009X
• DOI: 10.1124/dmd.117.075234

We evaluated the long-term stability of hepatocytes stored in the vapor phase of liquid nitrogen for their viability, cytochrome P450 (CYP) 1A2 activity, CYP3A4/5 activity, uridine diphosphate-glucuronosyl transferase (UGT) activity, sulfotransferase (SULT) activity, and CYP3A4/5 induction during 14 years of preservation. No substantial degradation of viability, CYP1A2 activity, UGT activity, or CYP3A4/5 induction was observed. CYP3A4/5 activity showed a slight decrease after 7 years of storage, and SULT activity gradually decreased during storage, although substantial activities remained even after 14 years. These results indicate that cryopreserved human hepatocytes can be stored stably for more than a decade with little or no change in viability, activity of drug-metabolizing enzymes, or CYP3A4/5 induction, and can be widely applicable to qualitative research in drug metabolism.