title: Long Term Liver Engraftment of Functional Hepatocytes Obtained from Germline Cell-Derived Pluripotent Stem Cells.
abstract: One of the major hurdles in liver gene and cell therapy is availability of ex vivo-expanded hepatocytes. Pluripotent stem cells are an attractive alternative. Here, we show that hepatocyte precursors can be isolated from male germline cell-derived pluripotent stem cells (GPSCs) using the hepatoblast marker, Liv2, and induced to differentiate into hepatocytes in vitro. These cells expressed hepatic-specific genes and were functional as demonstrated by their ability to secrete albumin and produce urea. When transplanted in the liver parenchyma of partially hepatectomised mice, Liv2-sorted cells showed regional and heterogeneous engraftment in the injected lobe. Moreover, approximately 50% of Y chromosome-positive, GPSC-derived cells were found in the female livers, in the region of engraftment, even one month after cell injection. This is the first study showing that Liv2-sorted GPSCs-derived hepatocytes can undergo long lasting engraftment in the mouse liver. Thus, GPSCs might offer promise for regenerative medicine.
authors: Institute for Biostructures and Bioimages (CNR), Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Sharmila
authors: S
authors: Fagoonee
authors: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Elvira Smeralda
authors: ES
authors: Famulari
authors: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Lorenzo
authors: L
authors: Silengo
authors: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Emanuela
authors: E
authors: Tolosano
authors: Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors: Fiorella
authors: F
authors: Altruda
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D002469:Cell Separation; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy; D005854:Germ Cells / Q000166:cytology; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008099:Liver / Q000502:physiology / Q000601:surgery; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D015415:Biomarkers; D014508:Urea