title: Decellularized liver scaffolds effectively support the proliferation and differentiation of mouse fetal hepatic progenitors.
abstract: Decellularized whole organs represent ideal scaffolds for engineering new organs and/or cell transplantation. Here, we investigate whether decellularized liver scaffolds provide cell-friendly biocompatible three-dimensional (3-D) environment to support the proliferation and differentiation of hepatic progenitor cells. Mouse liver tissues are efficiently decellularized through portal vein perfusion. Using the reversibly immortalized mouse fetal hepatic progenitor cells (iHPCs), we are able to effectively recellularize the decellularized liver scaffolds. The perfused iHPCs survive and proliferate in the 3-D scaffolds in vitro for 2 weeks. When the recellularized scaffolds are implanted into the kidney capsule of athymic nude mice, cell survival and proliferation of the implanted scaffolds are readily detected by whole body imaging for 10 days. Furthermore, epidermal growth factor (EGF) is shown to significantly promote the proliferation and differentiation of the implanted iHPCs. Histologic and immunochemical analyzes indicate that iHPCs are able to proliferate and differentiate to mature hepatocytes upon EGF stimulation in the scaffolds. The recellularization of the biomaterial scaffolds is accompanied with vascularization. Taken together, these results indicate that decullarized liver scaffolds effectively support the proliferation and differentiation of iHPCs, suggesting that decellularized liver matrix may be used as ideal biocompatible scaffolds for hepatocyte transplantation.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China; Department of Surgery, Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, Illinois, 60637.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Bing-Qiang
authors.initials: BQ
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.forename: Quan
authors.initials: Q
authors.lastname: Kang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.forename: Zhanyu
authors.initials: Z
authors.lastname: Yang
authors.forename: Huaizhi
authors.initials: H
authors.lastname: Wang
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Ni
authors.initials: N
authors.lastname: Tang
authors.forename: Jiahong
authors.initials: J
authors.lastname: Dong
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005333:Fetus / Q000166:cytology*; D057809:HEK293 Cells; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010477:Perfusion; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013370:Subrenal Capsule Assay; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D004815:Epidermal Growth Factor
keywords: cell transplantation; decellularized scaffolds; immortalized progenitors; liver progenitor cells; regenerative medicine; tissue engineering