| 研究実績の概要 |
Studies in vitro and in animal model were carried out complementary to optimize mesenchymal stem cells (MSCs) transplantation for benefits to treatment of glioblastoma (GBM) by enhancing anti-tumor effect in combination with GSK3β inhibitors and temozolomide (TMZ). For in vitro study, we examined the interaction between patient-derived GBM stem-like cells (SCs) and human adipose tissue-derived MSCs in the presence and absence of GSK3β inhibition and TMZ. I found that the interaction of MSCs with GBM-SCs is enhanced by a combined treatment by GSK3β inhibitor and that MSCs co-cultured with GBM-SCs participate in regulation of GBM stemness phenotype similar to that observed under GSK3β inhibition. For animal model study, we examined effects of intracranial transplantation of MSCs, neural-transdifferentiated MSCs and primary mouse neural stem cells (NSCs) against GBM in mice bearing mouse GBM cell lines or human GBM-SCs. Our experiments showed that transplantation of MSCs and GSK3β inhibition synergizes for treatment of experimental GBM and that monotherapy by intratumor infusion of a GSK3b inhibitor improve survival with tumor eradication in mouse GBM model. We also investigated biological mechanisms by which GSK3β regulate GBM stemness phenotype and determined that GSK3β inhibition decreases stem cell markers’ expression in GBM-SCs from patients.
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