Conditionally immortal neuroepithelial stem cell grafts reverse age-associated memory impairments in rats

In order to investigate the effects of stem cell grafts on water maze defic its in aged (22 month-old) rats, three groups of aged rats, assigned by pre -training latency scores to unimpaired, impaired control and impaired graft ed groups, were compared with young (five-month-old) controls, six to eight weeks after implantation of cells from the conditionally immortal Maudsley hippocampal stem cell line, clone 36 (MHP36 stem cell line), in the cortex , striatum and hippocampus. Grafted rats were substantially superior to the ir matched impaired aged controls, and learned to find the platform as rapi dly as unimpaired aged rats, although young controls were more efficient th an all aged groups in several measures of spatial search during training. O n the probe trial, however, aged rats with grafts showed significantly bett er recall of the precise position of the platform than any other group, inc luding young Controls, possibly indicating some perseveration. A further co mparison found that groups of unimpaired and moderately impaired aged rats showed far less improvement from water maze pre-training to acquisition pha ses than young controls, indicative of progressive deficits over time. Hist ological investigation showed that beta -galactosidase-positive MHP36 cells migrated widely from the implantation sites to infiltrate the striatal mat rix, all hippocampal fields and areas of the cortex. Grafted cells showed b oth astrocytic and neuronal morphologies, with cells of pyramidal and granu lar appearance in appropriate hippocampal strata. Taken together, these results indicate that neuroepithelial stem cell graft s extensively colonize the aged rat brain and substantially reverse progres sive cognitive decline associated with ageing. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.