Bone marrow stromal cells induce cell cycle arrest in reactive astrocytes in vitro

Transplantation of bone marrow stromal cells (BMSCs) reduces astrogliosis, decreases scar thickness and improves neurological functional recovery after brain damage. It is believed that transplanted BMSCs have a profound influence on astrocytes. To obtain the possible mechanism in their interaction, a co-culture system between BMSCs and astrocytes were set to investigate whether BMSCs could modulate cell cycle machinery in reactive astrocytes. The results obtained showed cell cycle regulatory proteins, cdk4 along with its activator cyclin D1, and PCNA increased while p27, an endogenous cyclin-dependent kinase inhibitor, deceased in glutamate-treated astrocytes in vitro. However, BMSCs influenced cell cycle elements in the cocultured astrocytes: cyclin D1, cdk 4 and PCNA were downregulated, while p27 was unregulated. Flow cytometry showed astrocytes in the S phase after glutamate incubation increased to 17.4±2.0% while restored to a level of 7.8±1.1% when cocultured with BMSCs. l-Canavanine, an inhibitor of inducible nitric oxide synthase, partially reversed the S phase to 11.3±0.4% in the cocultured astrocytes. These data indicated that BMSCs might inhibit the cell cycle control system in reactive astrocytes and nitric oxide signaling was involved in this process. The decline of astrogliosis conferred by BMSCs may derive from their effect of inhibiting the cell cycle progression in astrocytes.