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Studies in vitro and in animal model were carried out complementary to explore whether mesenchymal stem cells (MSCs) transplantation benefits to treatment of glioblastoma (GBM) by enhancing anti-tumor effect in combination with GSK3β inhibitors and temozolomide (TMZ). Our experiments showed that transplantation of MSCs and GSK3β inhibition synergizes for treatment of experimental GBM and that MSCs co-cultured with GBM cells participate in regulation of GBM stemness phenotype similar to that observed under GSK3β inhibition.
We examined the interaction between patient-derived GBM stem-like cells and adipose tissue-derived MSCs in the presence and absence of GSK3β inhibition and TMZ and its influence on GBM stemness phenotype. I found that the interaction of MSCs with GBM stem-like cells is enhanced by a combined treatment by GSK3β inhibitor. I have also observed by confocal time-lapse microscopy frequent phagocytosis-like cellular reactions enhanced by GSK3b inhibition of the patient-derived MSCs when they were interacting with primary GBM-SCs. These observations encouraged us to continue investigation of the biological mechanisms by which MSCs regulate GBM stemness phenotype under the control by GSK3βaddressing the role of cell-to-cell interactions including phagocytosis and local signals.
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