Neural stem cells: from cell biology to cell replacement

A large number of crippling neurological conditions result from the loss of certain cell populations from the nervous system through disease or injury, and these cells are not intrinsically replaced. Mounting evidence now suggests that replacement of depleted cell populations by transplantation may be of functional benefit in many such diseases. A diverse range of cell populations is vulnerable, and the loss of specific populations results in circumscribed deficits in different conditions. This diversity presents a considerable challenge if cell replacement therapy is to become widely applicable in the clinical domain, because each condition has specific requirements for the phenotype, developmental stage, and number of cells required. An ideal cell for universal application in cell replacement therapy would possess several key properties: it would be highly proliferative, allowing the ex vivo production of large numbers of cells from minimal donor material; it would also remain immature and phenotypically plastic such that it could differentiate into appropriate neural and glial cell types on, or prior to, transplantation. Critically, both proliferation and differentiation would be controllable. This review considers some of the evidence that stem cells exist in the central nervous system and that they may possess characteristics that make them ideal for broad application in cell replacement therapy.