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The influence of human fetal mesenchymal stem cells on glioma cell proliferation. The consequence of cellular crosstalk

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Abstract

The influence of mesenchymal stem cells (MSC) on the growth of various tumors is ambiguous. MSC derived from different tissues stimulate growth of some tumor types, but have a prominent antitumor affect on other tumors. It has been reported recently that the outcome may be determined by crosstalk between tumor cells and MSC. The aim of this study was to examine the impact of MSC derived from fetal tissues on glioma cell proliferation during prolonged coculturing. We have analyzed the proliferative activity of glioma cells exposed to conditioned medium (CM) from MSC derived from fetal bone marrow (FetMSC), fetal muscle (M-FetMSC), and CM from cocultures of the fetal MSC with U251MG glioma cells. The effect was compared with the influence of CM from adult dermal fibroblasts (DF). Using MTT assay, we found that CM both from the fetal MSC and adult DF (without coculturing with glioma cells) had no effect on U251MG and A172 glioma cell proliferation. However, CM from early cocultures (3–9 days) of U251MG cells with FetMSC or M-FetMSC exerted a stimulatory effect on U251MG cell proliferation while CM taken from the same cocultures later (15–21 days) inhibited the cell proliferation. Adult DF displayed a persistent stimulation of U251MG cell proliferative activity. Immunofluorescence analysis revealed declined expression of cell cycle protein cyclin D1 in U251MG cells after their treatment with CM from 21-day cocultures of U251MG cells with FetMSC or M-FetMSC. In contrast, CM from 21-day cocultures of U251MG cells with DF did not decrease cyclin D1 expression. These results show that the effect of fetal MSC on glioma cell proliferation is ambivalent. Stimulation of proliferative activity was observed in the early period of cocultivation; however, inhibition of glioma cell proliferation was registered after 3 weeks of their coculturing with fetal MSC. This is the first report showing reversion of tumor cell proliferative program during long-term coculturing with MSC. These data suggest that CM obtained at different time points of coculturing may be used in the modeling of prolonged cellular crosstalk.

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Abbreviations

DF:

dermal fibroblasts

CM:

conditioned medium

MSC:

mesenchymal stem cells

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  1. Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia

    I. A. Chistyakova & G. G. Poljanskaya

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  1. I. A. Chistyakova
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  2. G. G. Poljanskaya
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Correspondence to I. A. Chistyakova.

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Original Russian Text © I.A. Chistyakova, G.G. Poljanskaya, 2014, published in Tsitologiya, 2014, Vol. 56, No. 11, pp. 800–808.

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Chistyakova, I.A., Poljanskaya, G.G. The influence of human fetal mesenchymal stem cells on glioma cell proliferation. The consequence of cellular crosstalk. Cell Tiss. Biol. 9, 71–78 (2015). https://doi.org/10.1134/S1990519X15020042

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