title: Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.
abstract: The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093; Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093;
authors: Xuanyi
authors: X
authors: Ma
authors: Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093;
authors: Xin
authors: X
authors: Qu
authors: Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093;
authors: Wei
authors: W
authors: Zhu
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
authors: Yi-Shuan
authors: YS
authors: Li
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093;
authors: Suli
authors: S
authors: Yuan
authors: Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093;
authors: Hong
authors: H
authors: Zhang
authors: Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
authors: Justin
authors: J
authors: Liu
authors: Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA 92093;
authors: Pengrui
authors: P
authors: Wang
authors: Chemical Engineering Program, University of California, San Diego, La Jolla, CA 92093;
authors: Cheuk Sun Edwin
authors: CS
authors: Lai
authors: Department of Medicine, University of California, San Diego, La Jolla, CA 92093;
authors: Fabian
authors: F
authors: Zanella
authors: Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
authors: Gen-Sheng
authors: GS
authors: Feng
authors: Department of Medicine, University of California, San Diego, La Jolla, CA 92093;
authors: Farah
authors: F
authors: Sheikh
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093; shuchien@ucsd.edu chen168@eng.ucsd.edu.
authors: Shu
authors: S
authors: Chien
authors: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093; Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093; shuchien@ucsd.edu chen168@eng.ucsd.edu.
authors: Shaochen
authors: S
authors: Chen
mesh_terms: D000418:Albumins / Q000096:biosynthesis; D032701:Biomimetics / Q000379:methods; D062028:Bioprinting / Q000379:methods*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology* / Q000166:cytology; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000418:Albumins
keywords: 3D bioprinting; biomaterials; iPSC; in vitro hepatic model; tissue engineering