Bone marrow-derived mesenchymal stem cells expressing BMP2 suppress glioma stem cell growth and stemness through Bcl-2/Bax signaling.

ABSTRACT

Objectives: To find an effective molecule that controls glioma stem cell (GSC) proliferation and differentiation for the development of future therapeutic interventions against glioblastoma. Material and Methods: Bone marrow-derived mesenchymal stem cells (BMSCs) were infected with a lentiviral vector to express BMP2. Cell viability, cell counting, and tumor sphere formation assays, as well as flow cytometry, immunofluorescence staining, and Western blotting were used to investigate the effects of BMSC-BMP2 on GSCs. Results: The results of flow cytometry and the CKK-8 assay showed that BMSC-BMP2 induced GSC apoptosis while inhibiting proliferation. BMSC-BMP2 decreased GSC neurosphere formation and neurospheres' transverse and vertical diameter. Meanwhile, BMSC-BMP2 downregulated GSC Nanog and OCT4 expression levels, suggesting stemness inhibition. Western blotting showed that BMSC-BMP2 increased Bax protein expression and significantly decreased Bcl-2 protein expression. Accordingly, the Bcl-2/Bax ratio increased. Conclusion: BMSC-BMP2 could effectively inhibit GSC proliferation, induce GSC apoptosis, and decrease GSC stemness, thereby providing a novel strategy for treating malignant glioma.