Research Report 2010 - MDC

with murine hepatocytes showed morphologic similaritiesto hepatic progenitor cells and revealed high levelsof early endodermal and hepatic markers, measured bythe detection of AFP, SOX17, HNF4 and albumin transcripts.The in vivo properties of transplanted stem cells wereexamined regarding proliferation, engraftment and celldifferentiation after application into newborn andadult immunodeficient mice. Intrahepatic transplantationof undifferentiated embryonic stem cells into miceresulted in fast and multiple teratoma growth.Different liver injury models were established inNOD/SCID mice and characterized with biochemicalmethods. An increase of hepatic engraftment afterCD34 + cell transplantation was determined in a modelof chemically-induced liver injury.Transplanted human embryonic stem cells into immunodeficientmice differentiated into cells of the threegerm layers, including endodermal derived cells, asrevealed by real-time RT-PCR with marker expression forAFP, HNF3/4 alpha and CK19 as well as by histology.Furthermore, gene expression pattern demonstratedthat 1053 genes were up regulated more than 2 fold inthe teratomas compared to undifferentiated embryonicstem cells, including genes for neuronal developmentas well as for angiogenesis. The teratomas showed ahigh degree of similarity to those structures of embryonicstem cells cultivated and differentiated in 3-D perfusionbioreactors (cooperation with Charite Berlin).The established transplantation models are suitable forexamining the organ distribution and the regenerativepotential of stem cells.Selected PublicationsFichtner, I, Rolff, J, Soong, R, Hoffmann, J, Hammer, S, Sommer, A, Becker, M,Merk, J. (2008). Establishment of patient-derived non-small cell lungcancer xenografts as models for the identification of predictivebiomarkers. Clin. Cancer Res. 14, 6456-6468.Hoffmann, J, Fichtner, I, Lemm, M, Lienau, P, Hess-Stumpp, H, Rotgeri, A,Hofmann, B, Klar. U. (2009). Sagopilone crosses the blood-brain barrier invivo to inhibit brain tumor growth and metastases. Neuro. Oncol.11, 158-166.Rolff, J, Dorn, C, Merk, J, Fichtner, I. (2009). Response of patient-derivednon-small cell lung cancer xenografts to classical and targeted therapiesis not related to multidrug resistance markers. J. Oncol.doi:10.1155/2009/814140.Wenzel, J, Zeisig, R, Haider, W, Habedank, S, Fichtner I. (2009). Inhibition ofpulmonary metastasis in a human MT3 breast cancer xenograft modelby dual liposomes preventing intravasal fibrin clot formation. BreastCancer Res. Treat. In press.Wulf-Goldenberg, A, Eckert, K, Fichtner, I. (2008). Cytokine pretreatment ofCD34 + cord blood stem cells in vitro reduced long-term engraftment inNOD/SCID mice. Eur. J. Cell Biol. 87, 69-80.Cancer Research 139