Brain repair by cell replacement and regeneration

Not so long ago the adult brain was thought to be a slowly decaying organ, a sophisticated but flawed machine condemned to inevitable decline. Several studies now suggest that stem cells can be isolated and used to restore function in the adult brain. There is also recent evidence that neurons can be generated from endogenous cells after injury to the brain. We discuss here new data from Zhao et al. (1) in this issue of PNAS suggesting that dopamine neurons are continuously formed in the adult substantia nigra. These cells and regenerative responses might provide a path to functional recovery in neurodegenerative disease and brain injury.

In neurodegenerative diseases, a loss of specific cells causes patients to present with psychiatric or neurological symptoms. The prospect of replacing the missing or damaged cells is attractive. The loss of a specific type of dopamine neuron in the substantia nigra is a major feature of the pathology in Parkinson's disease. Embryonic tissue from this region, rich in dopamine neuroblasts, has been grafted to the striatum in Parkinson's patients. These clinical trials provide proof-of-principle for the cell replacement strategy in the human brain (2), but the technique is not ready for general use (3). What are the problems here? Is there really a prospect for regenerating the damaged brain? Here we discuss two fundamental issues for a regenerative approach to neurology: (i) Can we identify and acquire the cells of interest? (ii) Does the damaged brain allow regenerative responses?

There are major logistical difficulties with the routine clinical use of human cells or tissue. These problems are amplified when the tissue comes from a small region of the developing brain, such as the substantia nigra. The development of techniques to expand the precursors provides a possible solution. Self-renewing stem cells have been identified in …