Neural stem cell therapy in the aging brain: pitfalls and possibilities

As aging progresses, there is a decline in the brain's capacity to produce new neurons in the two neurogenic regions, the subventricular zone surrounding the lateral ventricles and the subgranular layer of the hippocampal dentate gyrus. The underlying cause of the declining neurogenesis is unknown, but is presumably related to age-related changes that occur during normal aging of the brain. It is exacerbated by age-related neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Stem cell-based therapy to replace lost and/or damaged cells in the aging brain is currently the focus of intense research. The two most promising approaches involve transplantation of exogenous tissue and promoting proliferation of endogenous cells. However, age-related changes in the brain environment, including elevated oxidative stress and accumulation of protein and lipid by-products, present several unique challenges that must be addressed before cell-based therapy can be used as a viable option. Although progress has been made toward replacement of lost cells and recovery of lost function, there are fundamental issues that need to be addressed for stem cell therapy to be successful in the aging brain. In this review, we focus on recent progresses made toward understand the biology of neural stem cells in the aging brain, as well as progress toward using stem cells to replace cells lost during disease.