INFLUENCE OF HUMAN FETAL MESENCHYMAL STEM CELLS ON GLIOMA CELL
PROLIFERATION. A CONSEQUENCE OF CELLULAR CROSSTALK
I.A. Chistyakova,1 G.G. Poljanskaya
Institute of Cytology RAS, St. Petersburg;
1 e-mail: ichi_spb@yahoo.com
The effect of mesenchymal stem cells (MSCs) on the growth of various tumors is ambiguous. MSCs derived
from different tissues stimulate growth of some tumor types and exert antitumor effects on the other. Several
recent reports have shown that crosstalk between tumor cells and MSCs contribute to these effects. The aim
of this work was to study the effects of MSCs derived from fetal tissues on the proliferative activity of glioma
cells in conditions of prolonged co-cultivation. We have analyzed the proliferative activity of glioma cells exposed
to conditioned medium (CM) from MSCs derived from fetal bone marrow (FetMSC) and fetal muscle
(M-FetMSC) as well as to CM from co-cultivation of the fetal MSCs with U251MG glioma cells. As a comparison,
the influence of CM from adult dermal fibroblasts (DFs) was examined in identical experiments. Using
MTT assay, we have found that CM from both the fetal MSCs and adult DFs (without their co-culturing with
glioma cells) had no effect on U251MG and A172 glioma cell proliferation. However, CM from early co-cultures
(3—9 days) of U251MG cells with FetMSC or M-FetMSC exerted stimulatory effect on U251MG cell proliferation
up to 2.3-fold increase, while CM obtained later from the same co-cultures (15—21 days) had inhibitory
effect on the proliferation up to arrest of cell division. Analogous experiments with adult DFs have revealed
a persistent stimulation of U251MG cell proliferative activity for all 21 days of co-culturing.
Immunofluorescence analysis revealed a reduction in the expression of cell cycle protein cyclin D1 in U251MG
cells after their treatment with CM taken from 21-days co-cultures of U251MG cells with FetMSC or
M-FetMSC. In contrast, CM from 21-days co-cultures of U251MG cells with DFs did not decrease the expression
of cyclin D1. These results show that fetal MSCs have dual effect on glioma cell proliferation. In spite of
the earlier stimulatory effect on the proliferative activity, prominent inhibition of glioma cell proliferation was
observed after three week co-culturing of glioma cells with fetal MSCs. This is the first report demonstrating
reversion of tumor cell proliferative program during co-culturing with MSCs for a long time. These data suggest
that CM obtained at different time points of cell co-culturing can be used in the modeling of prolonged cellular
crosstalk.
Key words: fetal mesenchymal stem cells, glioma cells, proliferation, conditioned medium, cellular
crosstalk
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