Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold
Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced plur...
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| Published in | Regenerative therapy Vol. 10; pp. 127 - 133 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.06.2019
Japanese Society for Regenerative Medicine Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2352-3204 2352-3204 |
| DOI | 10.1016/j.reth.2019.03.002 |
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| Abstract | Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold.
Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C.
After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium.
Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.
•Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold.•The recellularized liver expressed human liver-related markers ALB and CYP3A4.•The recellularized liver scaffold secreted human albumin.•This novel model shows potential for artificial whole liver transplantation. |
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| AbstractList | Introduction: Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Methods: Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C. Results: After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium. Conclusion: Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions. Keywords: Decellularized liver, Recellularization, Human iPSC, Hepatocyte, Artificial liver Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C. After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium. Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions. •Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold.•The recellularized liver expressed human liver-related markers ALB and CYP3A4.•The recellularized liver scaffold secreted human albumin.•This novel model shows potential for artificial whole liver transplantation. Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO (5%) cell incubator at 37 °C. After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin ( ) and genes, and secreted human ALB into the culture medium. Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions. • Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold. • The recellularized liver expressed human liver-related markers ALB and CYP3A4. • The recellularized liver scaffold secreted human albumin. • This novel model shows potential for artificial whole liver transplantation. Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold.INTRODUCTIONLiver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold.Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C.METHODSRat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C.After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium.RESULTSAfter 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium.Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.CONCLUSIONNovel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions. |
| Author | Ishii, Takamichi Fukumitsu, Ken Uemoto, Shinji Yamaoka, Ryoya Kotaka, Maki Ogiso, Satoshi Kawamoto, Hiroshi Miyauchi, Yuya Oshima, Yu Kawai, Takayuki Kojima, Hidenobu Osafune, Kenji Minami, Takahito Yasuchika, Kentaro Yasuda, Katsutaro |
| AuthorAffiliation | b Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan c Japanese Red Cross Wakayama Medical Center, 4-20 Komatsubara-dori, Wakayama City 640-8558, Japan a Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan |
| AuthorAffiliation_xml | – name: b Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – name: c Japanese Red Cross Wakayama Medical Center, 4-20 Komatsubara-dori, Wakayama City 640-8558, Japan – name: a Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan |
| Author_xml | – sequence: 1 givenname: Takahito surname: Minami fullname: Minami, Takahito organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 2 givenname: Takamichi surname: Ishii fullname: Ishii, Takamichi email: taishii@kuhp.kyoto-u.ac.jp organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 3 givenname: Kentaro surname: Yasuchika fullname: Yasuchika, Kentaro organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 4 givenname: Ken surname: Fukumitsu fullname: Fukumitsu, Ken organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 5 givenname: Satoshi surname: Ogiso fullname: Ogiso, Satoshi organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 6 givenname: Yuya surname: Miyauchi fullname: Miyauchi, Yuya organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 7 givenname: Hidenobu surname: Kojima fullname: Kojima, Hidenobu organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 8 givenname: Takayuki surname: Kawai fullname: Kawai, Takayuki organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 9 givenname: Ryoya surname: Yamaoka fullname: Yamaoka, Ryoya organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 10 givenname: Yu surname: Oshima fullname: Oshima, Yu organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 11 givenname: Hiroshi surname: Kawamoto fullname: Kawamoto, Hiroshi organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 12 givenname: Maki surname: Kotaka fullname: Kotaka, Maki organization: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 13 givenname: Katsutaro surname: Yasuda fullname: Yasuda, Katsutaro organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 14 givenname: Kenji orcidid: 0000-0001-7238-2763 surname: Osafune fullname: Osafune, Kenji organization: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan – sequence: 15 givenname: Shinji surname: Uemoto fullname: Uemoto, Shinji organization: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31032388$$D View this record in MEDLINE/PubMed |
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| Snippet | Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to... • Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold. • The recellularized liver expressed human liver-related markers ALB... Introduction: Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is... |
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| SubjectTerms | Artificial liver Decellularized liver Hepatocyte Human iPSC Original Recellularization |
| Title | Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold |
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