Z Gastroenterol 2011; 49 - P3_12
DOI: 10.1055/s-0030-1269627

Hepatic differentiation of adipose-derived mesenchymal stem cells reduces recruitment of immune cells after transplantation into livers of CCl4 treated mice

S Ehnert 1, C Eipel 2, K Abshagen 2, A Othman 3, C Seeliger 1, U Stöckle 1, B Vollmar 2, J Henstler 3, AK Nussler 1
  • 1Dept. of Traumatology, MRI, TU Munich, Munich Germany, Munich
  • 2Inst. für Experimentelle Chirurgie, Medizinische Fakultät, Universität Rostock, Rostock
  • 3Leibniz Research Centre for Working Environment and Human Factors, Dortmund

Transplantation of hepatocytes is a therapeutic approach for diverse acute and chronic liver diseases. As the availability of primary cells is limited, there exists an increasing demand for hepatocyte-like cells that can be obtained by stem cell technology. Among which adipose-derived mesenchymal stem cells (Ad-MSCs) represent a promising source, as they are easily assessable and can be obtained in sufficient amounts.

Human Ad-MSCs were isolated from different patients, with their informed consent according to ethical guidelines of the MRI. Hepatic differentiation was induced by addition of 5-azacytidine, FGF-4, dexamethasone, nicotinamide, ITS, HGF and EGF. After 18 days those hepatocyte-like cells (Ad-HLCs) were able to metabolize ammonium-chloride to urea and perform glucose metabolism comparable to primary human hepatocytes. Furthermore, phase I and II enzyme activities reached levels up to 80% of human hepatocytes. After labeling with red fluorescent dye DiI both Ad-HLCs and Ad-MSCs (0.5 * 106 cells/mouse) were transplanted into CCl4 treated C57/Bl6 or Scid/beige mice via injection into the spleen. After 4, 10 and 21 days mice were sacrificed and livers were analyzed for the presence of the injected cells by 3D confocal microscopy. Cells were found located within hepatic sinusoids, while a minor fraction particularly of the Ad-HLCs also revealed integration into parenchymal tissue. Transplanting undifferentiated Ad-MSCs led to a massive accumulation of immune cells within the livers of C57/Bl6 mice. In case of Ad-HLCs, significantly less immune cells were recruited.

Our data show that hepatic differentiation seems to protect Ad-MSCs to some extent from the mice’s immune reaction. Further investigation is necessary to investigate whether loss of surface markers on the differentiated Ad-MSCs allows the immune escape.

Transplantation of undifferentiated Ad-MSCs into C57/Bl6 causes a stronger immune reaction then transplantation of Ad-MSC-redived heptocyte-like cells.

Fig.1

cell therapy - hepatocyte-like cells - primary human hepatocytes