title: Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix.
abstract: There is currently no optimal system to expand and maintain the function of human adult hepatocytes in culture. Recent studies have demonstrated that specific tissue-derived extracellular matrix (ECM) can serve as a culture substrate and that cells tend to proliferate and differentiate best on ECM derived from their tissue of origin. The goal of this study was to investigate whether three-dimensional (3D) ECM derived from porcine liver can facilitate the growth and maintenance of physiological functions of liver cells. Optimized decellularization/oxidation procedures removed up to 93% of the cellular components from porcine liver tissue and preserved key molecular components in the ECM, including collagen-I, -III, and -IV, proteoglycans, glycosaminoglycans, fibronectin, elastin, and laminin. When HepG2 cells or human hepatocytes were seeded onto ECM discs, uniform multi-layer constructs of both cell types were formed. Dynamic culture conditions yielded better cellular infiltration into the ECM discs. Human hepatocytes cultured on ECM discs expressed significantly higher levels of albumin over a 21-day culture period compared to cells cultured in traditional polystyrene cultureware or in a collagen gel "sandwich". The culture of hepatocytes on 3D liver-specific ECM resulted in considerably improved cell growth and maintained cell function; therefore, this system could potentially be used in liver tissue regeneration, drug discovery or toxicology studies.
authors: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors: Ren
authors: R
authors: Lang
authors: Matthew M
authors: MM
authors: Stern
authors: Leona
authors: L
authors: Smith
authors: Yan
authors: Y
authors: Liu
authors: Shantaram
authors: S
authors: Bharadwaj
authors: Guihua
authors: G
authors: Liu
authors: Pedro M
authors: PM
authors: Baptista
authors: Christopher R
authors: CR
authors: Bergman
authors: Shay
authors: S
authors: Soker
authors: James J
authors: JJ
authors: Yoo
authors: Anthony
authors: A
authors: Atala
authors: Yuanyuan
authors: Y
authors: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry* / Q000648:ultrastructure; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000166:cytology*; D008422:Materials Testing; D016062:Porosity; D034421:Sus scrofa
chemical_list: D001672:Biocompatible Materials