In vitro production of functionally mature hepatocytes from prospectively isolated hepatic stem cells.
Hepatocyte transplantation and artificial organ hepatic support require a number of functionally mature hepatocytes. However, their growth activity and functional behaviors are much smaller in culture after isolation from the liver. We examined whether continuously differentiating hepatocytes from multipotent hepatic stem cells that were isolated by using flow cytometry and propagated clonally in culture could be a source of clinical application. They actually gave rise to cells that were functionally equal to mature hepatocytes found in the adult liver, which secreted albumin into culture medium and metabolized harmful ammonium into urea. These data suggest that stem cell-derived hepatocytes are a useful cell source for developing therapeutic strategies, such as cell transplantation, gene therapy, and artificial liver organ to treat various liver disorders.
Suzuki
Atsushi
A
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Nakauchi
Hiromitsu
H
Taniguchi
Hideki
H
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014508:Urea / Q000378:metabolism / Q000494:pharmacology
D000418:Albumins; D000644:Quaternary Ammonium Compounds; D017228:Hepatocyte Growth Factor; D014508:Urea