of the Max - MDC

Structure of the Group
Group Leader
Dr. Iduna Fichtner
Scientists
Dr. Michael Becker
Dr. Klaus Eckert
Dr. Reiner Zeisig
Dr. Diana Behrens
Graduate Students
Jana Rolff
Annika Wulf
Marlen Keil
Jane Wenzel
Andrea Hoffmann
Technical Assistants
Monika Becker
Margit Lemm
Claudia Neumann
Secretariat
Sylvia Schulz
brane enables cluster formation (Figure 2) as a prerequisite
to accumulate ligands at the binding site to the endothelial
membrane. Finally it could be demonstrated that tumor cells
with a more fluid membrane are more potent for an engraftment
and formation of metastatic nodules.
Potential of adult and embryonic human stem
cells for liver regeneration
In previous studies, cytokine effects on CD34 + cord blood
stem cell proliferation, differentiation in vitro and in vivo
were investigated. To validate the contribution of direct
cell-cell communication of stem cells with hepatocytes, coculture
systems were established. Using dye transfer techniques
and video imaging of labelled cells, stem cell interactions
with cultivated hepatocyte cell lines and primary
mouse hepatocytes were quantified and the expression of
Connexin 43 and 32 was analyzed.
For monitoring stem cell engraftment in vivo, a panel of
viral and non-viral transfection methods using vector systems
with GFP and luciferase as reporter genes were developed
for in vivo bioluminescence imaging of stem cells and
revealed a dose dependent accumulation in the region of
the bone marrow.
For in vivo studies, using the highly immunodeficient
NOD/SCID IL-2R-γ- mouse strain, a significantly higher
CD34 + cell engraftment in bone marrow, spleen and liver
after systemic cell transplantation was measured compared
to NOD/SCID mice. Organ specific intrahepatic application
of CD34 + cells into newborn NOD/SCID IL-2R-γ-mice revealed
high engraftment rates and lineage specific B-and T-cell differentiation
in mouse organs.
In parallel, different liver injury model were established and
characterized histological, by liver enzyme marker and
endogenous liver stem cell induction. Transplantation of
undifferentiated CD34 + cells into partially hepatectomiced
mice in the presence of monocrotaline led to high stem cell
engraftment rates in mouse organs.
The pluripotency of embryonic mouse stem cells was evaluated
by teratoma formation in syngeneic mice. Using different
routes of stem cell transplantation, germ layer structures
of endodermal, mesodermal and ectodermal differentiated
cells were found in teratoma and characterized histologically.
Selected Publications
Behrens, D, Gill, JH, and Fichtner, I. (2007). Loss of tumorigenicity
of stably ERβ-transfected MCF-7 breast cancer cells.
Molecular and Cellular Endocrinology 274, 19-29.
Behrens, D, Lykkesfeldt, AF, Fichtner, I. (2007). The mTOR
pathway inhibitor RAD001 (everolimus) is highly efficious in
tamoxifen-sensitive and –resistant breast cancer xenografts.
Target. Oncol. 2, 135-144.
Keil, C, Zeisig, R, Fichtner, I. (2005). Effect of surface modified
liposomes on the aggregation of platelets and tumor cells.
Thromb. Haemost. 94, 404-11.
Einsiedel, HG, Kawan, L, Eckert, C, Witt, O, Fichtner, I, Henze, G,
and Seeger, K. (2006). Histone deacetylase inhibitors have
antitumor activity in two NOD/SCID mouse models of B-cell precursor
childhood acute lymphoblastic leukemia. Leukemia 20,
1435-1436.
Shalapour, S, Zelmer, A, Pfau, M, Moderegger, E, Costa-
Blechschmidt, C, van Landeghem, FK, Taube, T, Fichtner, I,
Bührer, C, Henze, G, Seeger, K, and Wellmann, S. (2006). The
thalidomide analogue, CC-4047, induces apoptosis signaling
and growth arrest in childhood acute lymphoblastic leukemia
cells in vitro and in vivo. Clin. Cancer Res. 12, 5526-5532.
Zeisig, R, Koklic, T, Wiesner B, Fichtner I, Sentjurc M. (2007).
Increase in fluidity in the membrane of MT3 breast cancer cells
correlates with enhanced cell adhesion in vitro and increased
lung metastasis in NOD/SCID mice. Arch Biochem Biophys. 459,
98-106.
Patent Applications
Zeisig, R, Fichtner, I: Pharmazeutische Zubereitung zur
Bekämpfung von Metastasen. DE 10 2007 008 484.8.,
filed on 19.02.2007
Figure 2. Cluster formation of sialyl
LewisA ligands in the membrane of
MT3 breast cancer cells: Projection of a
3D reconstruction of a Z-stack of two
stacked MT3 breast cancer cells obtained
by confocal laser scanning microscopy.
Shown is the ligand distribution
in the membrane after fluorescence
staining of sialyl LewisA (green)
Cancer Research 145