title: Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage.
abstract: ESCs are a potential cell source for cell therapy. However, there is no evidence that cell transplantation using ESC-derived hepatocytes is therapeutically effective. The main objective of this study was to assess the therapeutic efficacy of the transplantation of ESC-derived endodermal cells into a liver injury model. The beta-galactosidase-labeled mouse ESCs were differentiated into alpha-fetoprotein (AFP)-producing endodermal cells. AFP-producing cells or ESCs were transplanted into transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Selective damage was induced in the recipient hepatocytes by the administration of DT. Although the transplanted AFP-producing cells had repopulated only 3.4% of the total liver mass 7 days after cell transplantation, they replaced 32.8% of the liver by day 35. However, these engrafted cells decreased (18.3% at day 40 and 7.9% at day 50) after the cessation of DT administration, and few donor cells were observed by days 60-90. The survival rate of the AFP-producing cell-transplanted group (66.7%) was significantly higher in comparison with that of the sham-operated group (17.6%). No tumors were detected by day 50 in the AFP-producing cell-transplanted group; however, splenic teratomas did form 60 days or more after transplantation. ESC transplantation had no effect on survival rates; furthermore, there was a high frequency of tumors in the ESC-transplanted group 35 days after transplantation. In conclusion, this study demonstrates, for the first time, that ESC-derived endodermal cells improve the survival rates after transplantation into mice with induced hepatocellular injury. Disclosure of potential conflicts of interest is found at the end of this article.
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Takamichi
authors: T
authors: Ishii
authors: Kentaro
authors: K
authors: Yasuchika
authors: Takafumi
authors: T
authors: Machimoto
authors: Naoko
authors: N
authors: Kamo
authors: Junji
authors: J
authors: Komori
authors: Sayuri
authors: S
authors: Konishi
authors: Hirofumi
authors: H
authors: Suemori
authors: Norio
authors: N
authors: Nakatsuji
authors: Michiko
authors: M
authors: Saito
authors: Kenji
authors: K
authors: Kohno
authors: Shinji
authors: S
authors: Uemoto
authors: Iwao
authors: I
authors: Ikai
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D017093:Liver Failure / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010534:Peritoneal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013160:Splenic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D000509:alpha-Fetoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000509:alpha-Fetoproteins