title: Reconstruction of 3D stacked hepatocyte tissues using degradable, microporous poly(d,l-lactide-co-glycolide) membranes.
abstract: There is great demand for constructing well-organized three-dimensional (3D) tissues in vitro. Here, we developed a 3D stacked culture method using biodegradable poly(d,l-lactide-co- glycolide) (PLGA) membranes with defined topography. Pore size and porosity of the membranes can be controlled by changing the moisture content during fabrication. The optimized membrane served as a scaffold to manipulate small hepatocyte (SH) layers when they were stacked, while it degraded after stacking, resulting in the reorganization of the cells into a 3D stacked structure. Immunofluorescent staining for domain markers of cell polarity and electron microscopy confirmed that the cells in the 3D stacked structures recovered polarity. Furthermore, the cells exhibited improved liver-specific function as compared with cells in a monolayer. This 3D stacked culture may enable reconstruction of multilayered hepatic tissues with highly differentiated functions in vitro.
authors.affiliation: Center for System Integration Engineering, School of Integrated Design Engineering, Keio University, 3-1-14-1, Kohoku, Yokohama 223 0061, Japan. kasuya@sudo.sd.keio.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Kasuya
authors.forename: Ryo
authors.initials: R
authors.lastname: Sudo
authors.forename: Ryu
authors.initials: R
authors.lastname: Tamogami
authors.forename: Genta
authors.initials: G
authors.lastname: Masuda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mitaka
authors.forename: Mariko
authors.initials: M
authors.lastname: Ikeda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanishita
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D009928:Organ Specificity / Q000187:drug effects; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid