The identification of stem cells in the fetal and adult mammalian brain has many scientific and clinical consequences. Evidence of a common stem cell generating the central and peripheral nervous system will be presented. As stem cells can be obtained in large numbers, they provide ideal systems to analyze how extracellular signals act to control stem cell differentiation. Analysis of CNT/LIF and BMP activated mechanisms in fetal and adult central nervous system stem cells will be discussed. Novel pathways will be described that control precursor cell identity, proliferation, and differentiation.
It is important to determine whether stem cells give rise to functional neurons. A signal loop between neurons and glia that activates neurotrophin release and controls the early steps in synaptic differentiation has been defined. Distinct neurotrophins control the balance between glutamatergic and γ-aminobutyric acid–ergic synaptic transmission. Neurotrophins have the same effects on synapse activation on neurons derived from hippocampal stem cells. This result suggests that hippocampal stem cells generate appropriate functional neuron types.
Knowledge of the events controlling the birth and activity-dependent death of neurons has important clinical potential. Experiments in tissue culture and in animal models will be used to illustrate how control of the origins of neuronal and glial cells may give new insight into Parkinson disease, Alzheimer disease, and demyelinating disease. New evidence will be presented suggesting that stem cell technology will also play a significant role in cardiac and endocrine disease. These technologies will promote the development of transplant therapies and make major contributions to drug discovery. The ability to manipulate stem cells will allow us to build organs and move toward understanding the complex functions of multicellular arrays in health and disease.