Antitumor Activity of Rat Mesenchymal Stem Cells during Direct or Indirect Co-Culturing with C6 Glioma Cells

被引：8

作者：

Gabashvili, A. N. ^{[1
]}

Baklaushev, V. P. ^{[1
,3
]}

Grinenko, N. F. ^{[2
]}

Mel'nikov, P. A. ^{[1
]}

Cherepanov, S. A. ^{[1
]}

Levinsky, A. B. ^{[1
]}

Chehonin, V. P. ^{[1
,2
]}

机构：

[1] NI Pirogov Natl Res Med Univ, Med Biol Fac, Dept Med Nanobiotechnol, Moscow, Russia

[2] Minist Hlth Russian Federat, VP Serbsky Fed Med Res Ctr Psychiat & Narcol, Dept Fundamental & Appl Neurobiol, Moscow, Russia

[3] Fed Med Biol Agcy, Fed Res & Clin Ctr, Moscow, Russia

来源：

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE | 2016年 / 160卷 / 04期

基金：

俄罗斯基础研究基金会;

关键词：

mesenchymal stem cells; glioblastoma multiforme; C6; glioma; conditioned medium; NEURAL PRECURSOR CELLS; TUMOR-CELLS; BRAIN; GROWTH; SUPPRESSES; PROGENITOR; INVASION;

D O I：

10.1007/s10517-016-3211-y

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The tumor-suppressive effect of rat mesenchymal stem cells against low-differentiated rat C6 glioma cells during their direct and indirect co-culturing and during culturing of C6 glioma cells in the medium conditioned by mesenchymal stem cells was studied in an in vitro experiment. The most pronounced antitumor activity of mesenchymal stem cells was observed during direct co-culturing with C6 glioma cells. The number of live C6 glioma cells during indirect co-culturing and during culturing in conditioned medium was slightly higher than during direct co-culturing, but significantly differed from the control (C6 glioma cells cultured in medium conditioned by C6 glioma cells). The cytotoxic effect of medium conditioned by mesenchymal stem cells was not related to medium depletion by glioma cells during their growth. The medium conditioned by other "non-stem" cells (rat astrocytes and fibroblasts) produced no tumor-suppressive effect. Rat mesenchymal stem cells, similar to rat C6 glioma cells express connexin 43, the main astroglial gap junction protein. During co-culturing, mesenchymal stem cells and glioma C6 cells formed functionally active gap junctions. Gap junction blockade with connexon inhibitor carbenoxolone attenuated the antitumor effect observed during direct co-culturing of C6 glioma cells and mesenchymal stem cells to the level produced by conditioned medium. Cell-cell signaling mediated by gap junctions can be a mechanism of the tumor-suppressive effect of mesenchymal stem cells against C6 glioma cells. This phenomenon can be used for the development of new methods of cell therapy for high-grade malignant gliomas.

引用

页码：519 / 524

页数：6

共 30 条

[1] Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas [J].

Aboody, KS ;

Brown, A ;

Rainov, NG ;

Bower, KA ;

Liu, SX ;

Yang, W ;

Small, JE ;

Herrlinger, U ;

Ourednik, V ;

Black, PM ;

Breakefield, XO ;

Snyder, EY .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12846-12851

[2] Neural Progenitor and Hemopoietic Stem Cells Inhibit the Growth of Low-Differentiated Glioma [J].

Baklaushev, V. P. ;

Grinenko, N. F. ;

Savchenko, E. A. ;

Bykovskaya, S. N. ;

Yusubalieva, G. M. ;

Viktorov, I. V. ;

Bryukhovetskii, A. S. ;

Bryukhovetskii, I. S. ;

Chekhonin, V. P. .

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE, 2012, 152 (04) :497-503

[3] Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy [J].

Barresi, V ;

Belluardo, N ;

Sipione, S ;

Mudó, G ;

Cattaneo, E ;

Condorelli, DF .

CANCER GENE THERAPY, 2003, 10 (05) :396-402

[4] High levels of connexin 43 mRNA in high grade astrocytomas. Study of 32 cases with in situ hybridization [J].

Caltabiano, Rosario ;

Torrisi, Antonietta ;

Condorelli, Daniele ;

Albanese, Vincenzo ;

Lanzafame, Salvatore .

ACTA HISTOCHEMICA, 2010, 112 (06) :529-535

[5] Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells [J].

Chirasani, Sridhar Reddy ;

Sternjak, Alexander ;

Wend, Peter ;

Momma, Stefan ;

Campos, Benito ;

Herrmann, Ilaria M. ;

Graf, Daniel ;

Mitsiadis, Thimios ;

Herold-Mende, Christel ;

Besser, Daniel ;

Synowitz, Michael ;

Kettenmann, Helmut ;

Glass, Rainer .

BRAIN, 2010, 133 :1961-1972

[6] Functionally Active Gap Junctions between Connexin 43-Positive Mesenchymal Stem Cells and Glioma Cells [J].

Gabashvili, A. N. ;

Baklaushev, V. P. ;

Grinenko, N. F. ;

Levinskii, A. B. ;

Mel'nikov, P. A. ;

Cherepanov, S. A. ;

Chekhonin, V. P. .

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE, 2015, 159 (01) :173-179

[7] Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival [J].

Glass, R ;

Synowitz, M ;

Kronenberg, G ;

Walzlein, JH ;

Markovic, DS ;

Wang, LP ;

Gast, D ;

Kiwit, JRR ;

Kempermann, G ;

Kettenmann, H .

JOURNAL OF NEUROSCIENCE, 2005, 25 (10) :2637-2646

[8]

Gnecchi Massimiliano, 2009, V482, P281, DOI 10.1007/978-1-59745-060-7_18

[9] Gap junctional complexes:: From partners to functions [J].

Herve, Jean-Claude ;

Bourmeyster, Nicolas ;

Sarrouilhe, Denis ;

Duffy, Heather S. .

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 2007, 94 (1-2) :29-65

[10] METABOLISM OF 5-FLUOROCYTOSINE TO 5-FLUOROURACIL IN HUMAN COLORECTAL TUMOR-CELLS TRANSDUCED WITH THE CYTOSINE DEAMINASE GENE - SIGNIFICANT ANTITUMOR EFFECTS WHEN ONLY A SMALL PERCENTAGE OF TUMOR-CELLS EXPRESS CYTOSINE DEAMINASE [J].

HUBER, BE ;

AUSTIN, EA ;

RICHARDS, CA ;

DAVIS, ST ;

GOOD, SS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (17) :8302-8306

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