title: Decellularized Liver Extracellular Matrix as Promising Tools for Transplantable Bioengineered Liver Promotes Hepatic Lineage Commitments of Induced Pluripotent Stem Cells.
abstract: Liver transplantation is the last resort for liver failure patients. However, due to the shortage of donor organs, bioengineered liver generated from decellularized whole liver scaffolds and induced pluripotent stem cell (iPSC)-derived hepatocytes (iPSC-Heps) is being studied as an alternative approach to treat liver disease. Nevertheless, there has been no report on both the interaction of iPSC-Heps with a liver extracellular matrix (ECM) and the analysis of recellularized iPSC-Heps into the whole liver scaffolds. In this study, we produced porcine iPSC-Heps, which strongly expressed the hepatic markers α-fetoprotein and albumin and exhibited hepatic functionalities, including glycogen storage, lipid accumulation, low-density lipoprotein uptake, and indocyanine green metabolism. Supplementation of ECM from porcine decellularized liver containing liver-derived growth factors stimulated the albumin expression of porcine iPSC-Heps during differentiation procedures. The iPSC-Heps were reseeded into decellularized liver scaffolds, and the recellularized liver was cultured using a continuous perfusion system. The recellularized liver scaffolds were transplanted into rats for a short term, and the grafts expressed hepatocyte markers and did not rupture. These results provide a foundation for development of bioengineered liver using stem cell and decellularized scaffolds.
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|2 School of Veterinary Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Kyung-Mee
authors.initials: KM
authors.lastname: Park
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|2 School of Veterinary Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Kamal Hany
authors.initials: KH
authors.lastname: Hussein
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|3 School of Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Hong
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|4 School of Biomedical Technology, Kangwon National University , Chuncheon, Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Ahn
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|3 School of Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Yang
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|3 School of Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: 5 School of Veterinary Medicine, Seoul National University , Seoul, Korea.
authors.forename: Oh-Kyeong
authors.initials: OK
authors.lastname: Kweon
authors.affiliation: 6 Departments of Medicine/GI Unit, Massachusetts General Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Byeong-Moo
authors.initials: BM
authors.lastname: Kim
authors.affiliation: 1 Stem Cell Institute-KNU, Kangwon National University , Chuncheon, Korea.|2 School of Veterinary Medicine, Kangwon National University , Chuncheon, Korea.
authors.forename: Heung-Myong
authors.initials: HM
authors.lastname: Woo
mesh_terms: D000818:Animals; D057005:Bioengineering / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017207:Rats, Sprague-Dawley; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins