OBJECTIVE: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated. METHODS AND RESULTS: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of immunodeficient Pfp/Rag2-/- mice with or without prior hepatocyte differentiation in vitro. Donor-derived human cells engrafted in the mouse host liver predominantly in the periportal region of the liver lobule. They expressed HepPar1 and albumin, typical features of differentiated human hepatocytes, in the otherwise negative mouse liver background. Engraftment was significantly more efficient using hAT-MSCs pre-differentiated to hepatocyte-like cells in vitro as compared with undifferentiated cells. CONCLUSIONS: Pre-differentiation of human MSCs from adipose tissue into hepatocyte-like cells in vitro facilitates long term functional hepatic integration in vivo.
OBJECTIVE: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated. METHODS AND RESULTS: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4). Transgenic expression of green fluorescent protein emerged upon hepatocyte differentiation when driven by the hepatocyte-specific promoter of the cytosolic phosphoenolpyruvate carboxykinase gene but was constitutive from the ubiquitin gene promoter. Human AT-MSCs were transplanted into livers of immunodeficient Pfp/Rag2-/- mice with or without prior hepatocyte differentiation in vitro. Donor-derived human cells engrafted in the mouse host liver predominantly in the periportal region of the liver lobule. They expressed HepPar1 and albumin, typical features of differentiated human hepatocytes, in the otherwise negative mouse liver background. Engraftment was significantly more efficient using hAT-MSCs pre-differentiated to hepatocyte-like cells in vitro as compared with undifferentiated cells. CONCLUSIONS: Pre-differentiation of human MSCs from adipose tissue into hepatocyte-like cells in vitro facilitates long term functional hepatic integration in vivo.
Authors: Karen Bieback; Patrick Wuchter; Daniel Besser; Werner Franke; Matthias Becker; Michael Ott; Martin Pacher; Nan Ma; Christof Stamm; Harald Klüter; Albrecht Müller; Anthony D Ho Journal: J Mol Med (Berl) Date: 2012-05-31 Impact factor: 4.599
Authors: Andreas K Nussler; Katrin Zeilinger; Lilianna Schyschka; Sabrina Ehnert; Jörg C Gerlach; Xueying Yan; Serene M L Lee; Maren Ilowski; Wolfgang E Thasler; Thomas S Weiss Journal: J Mater Sci Mater Med Date: 2011-04-03 Impact factor: 3.896
Authors: Anton Selich; Jannik Daudert; Ralf Hass; Friederike Philipp; Constantin von Kaisenberg; Gabi Paul; Kerstin Cornils; Boris Fehse; Susanne Rittinghausen; Axel Schambach; Michael Rothe Journal: Stem Cells Transl Med Date: 2016-03-31 Impact factor: 6.940