The morphology, functionality, and longevity of a novel all human hepatic cell-based tri-culture system.

Autor: Weaver JR; Institute of Regenerative Medicine, LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453, United States of America., Odanga JJ; Institute of Regenerative Medicine, LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453, United States of America., Wolf KK; Research and Development, LifeSciences, LifeNet Health, 6 Davis Drive, Research Triangle Park, NC 27709, United States of America., Piekos S; Non-Clinical DMPK, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States of America., Biven M; Corteva AgriScience, 9330 Zionsville Road, Indianapolis, IN 46268, United States of America., Taub M; Non-Clinical DMPK, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States of America., LaRocca J; Corteva AgriScience, 9330 Zionsville Road, Indianapolis, IN 46268, United States of America., Thomas C; Non-Clinical DMPK, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States of America., Byer-Alcorace A; Non-Clinical DMPK, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States of America., Chen J; Institute of Regenerative Medicine, LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453, United States of America., Lee JB; Institute of Regenerative Medicine, LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453, United States of America. Electronic address: Jungbok_lee@lifenethealth.org., LeCluyse EL; Research and Development, LifeSciences, LifeNet Health, 6 Davis Drive, Research Triangle Park, NC 27709, United States of America. Electronic address: Edward_lecluyse@lifenethealth.org.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Feb; Vol. 86, pp. 105504. Date of Electronic Publication: 2022 Oct 23.
DOI: 10.1016/j.tiv.2022.105504
Abstrakt: There remains a significant need for a convenient, phenotypically stable long-term culture platform for primary human hepatocytes (PHHs) for use in pharmacological and toxicological applications. Conventional in vitro models are often inconvenient, burdensome to use, and unable to support a multitude of donor lots or maintain PHH structural and functional properties over extended time. To address these limitations, an all-human cell-based hepatic tri-culture system (HTCS) has been developed comprised of frozen vials of PHHs and feeder cells. Qualified PHHs exhibited healthy morphological characteristics for ≥30 days. Extensive anastomosing networks of bile canaliculi with tight and gap junctions were established early and remained stable and functional throughout the culture period. After 5 culture days, albumin, urea, and basal Phase 1 and Phase 2 metabolic functions were stable for at least 2 weeks and significantly higher in the HTCS PHHs compared to sandwich monoculture PHHs. Induction of CYP functional activity by prototypical receptor agonists was stable after 4 days for at least 2 weeks. Gene expression of Alb and various CYPs in the HTCS PHHs was significantly higher compared to sandwich monoculture PHHs. The HTCS represents a convenient, phenotypically stable, all-human PHH culture platform for pharmacological and toxicological applications.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JW, JO, KW, JC, JL, and EL are employed by LifeNet Health. SP, MT, CT, and ABA are employed by Boehringer Ingelheim Pharmaceuticals, Inc. MB and JLR are employed by Corteva AgriScience.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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