Migration of A7 immortalized astrocytic cells grafted into the adult rat striatum

Abstract

The A7 cell line is an SV40 large T antigen-immortalized astrocyte cell line produced from the neonatal rat optic nerve. Previous studies have demonstrated that A7 cells provide a favorable environment for the survival and growth of cultured neurons and can also stimulate axonal growth after grafting into the rat striatum. The current study was designed to investigate whether A7 cells grafted into adult rat striatum can migrate away from the implantation site. A7 cells were labelled in culture by incorporation of bromodeoxyuridine (BrdU) or by expression of an alkaline phosphatase transgene. The labelled cells were then transplanted into the left striatum of normal adult rats by introducing a blunt-end 22 gauge needle through a trephine hole. The rats were euthanized at periods of up to 30 days after grafting. The A7 cells did not appear to alter the cytoarchitecture of the surrounding brain parenchyma. Labelled A7 cells were observed in both gray and white matter areas, and many were located in areas free of damage due to the implantation procedure. The migration of the BrdU-labelled A7 cells with respect to the implantation needle track was determined on coronal sections. The radial migration distance from the needle tract was similarly determined on horizontal sections. A7 cells migrated progressively longer distances with increasing survival time of the animals: The largest migration distance (1,125 +/- 52 microns) occurred at 30 days after grafting with an estimated migration rate of 31 microns per day. There was no significant directional polarity in the migration of these cells within the striatum. Some of the labelled A7 nuclear profiles were associated with blood vessels, some appeared to be associated with fiber bundles within the striatum, and some were found within the gray matter without apparent association with any anatomical structure. These results demonstrate that A7 immortalized astrocytic cells migrate away from a single implantation site following grafting into the adult rat striatum to populate a large area of the striatum.