Bone marrow stromal cells induce BMP2/4 production in oxygen-glucose-deprived astrocytes, which promotes an astrocytic phenotype in adult subventricular progenitor cells
Abstract
Bone morphogenetic proteins (BMPs) affect cell proliferation and differentiation. Astrocytes in ischemic brain are highly responsive to bone marrow stromal cell (BMSC) treatment. We investigated the effects of BMSCs on astrocytes cultured under oxygen- and glucose-deprived conditions, which in part simulate in vivo stroke conditions, to test the hypothesis that BMSCs alter astrocytic expression of BMPs which may contribute to neurological functional recovery of stroke. Quantitative real-time RT-PCR showed that the expression of BMP2/4 mRNAs decreased within ischemic astrocytes, In contrast, BMP2/4 mRNA was significantly increased after cocultured with BMSCs. Western blotting also confirmed this increase at the protein level in the medium of ischemic astrocytes after coculture with BMSCs. As a source of neural stem and progenitor cells, cultured subventricular zone (SVZ) neurospheres exposed to medium obtained from ischemic astrocytes cocultured with BMSCs were significantly enriched in cells expressing the astrocytic marker glial fibrillary acidic protein (GFAP), but not at the expense of beta-III-tubulin-positive SVZ neuroblasts. The expression of BMP2/4 subsequently increased the phosphorylation of downstream effector Smad1 a...Continue Reading
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