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Unformatted text preview: SECTION EDITOR: DAVID E. PLEASURE, MD Progenitor Cell Biology Implications for Neural Regeneration Mark F. Mehler, MD; John A. Kessler, MD A few brief years ago, damage to the central nervous system was generally perceived to be irreparable, and loss of neurons was largely viewed as an irreversible process. However, major advances in the study of neural progenitor cells have altered these perceptions, and rational approaches to the repair of the damaged nervous system using transplanted progenitor cells now seem feasible. This review will discuss the basic biology of neural progenitor cells, the mechanisms regulating the generation of neurons and glia from these cells, and the techniques that are available for preparing such cells for transplantation into the nervous system. The potential uses for these cells in treating neurologic disease will then be reviewed, and the theoretical and tech- nical problems that may be encountered will be discussed. Arch Neurol. 1999;56:780-784 NEURAL PROGENITOR CELLS The major cellular elements of the central nervous system (CNS) (neurons, astro- cytes,andoligodendrocytes)arisefromspe- cialized germinative regions derived from the inner lining of the neural tube. 1-3 These zones extend from periventricular regions of the telencephalon to the central canal of the spinal cord. They initially consist of a pseudostratified epithelium (ventricular zone [VZ]) during early embryonic life that contains progenitor cells with a range of neurallineagepotentials. 1-4 Duringlaterem- bryogenesis, the VZ gives rise to second- ary paramedian subventricular zones that persistasrestrictedzonesintotheadultstate (eg,subependymalregionofthelateralven- tricle). 1-5 Neuronsandradialgliaaretheini- tialcelltypesgeneratedwithintheearlyem- bryonic VZ. 6,7 By contrast, astrocytes and oligodendrocytes are generated during the late embryonic and the early postnatal pe- riods within regional cortical subventricu- lar zones. 8 In addition, ongoing areas of neurogenesisduringlatepostnatalandadult life occur in the olfactory bulb, in the den- tate gyrus of the hippocampus, and in the Purkinje cell layer of the cerebellum. 1,9 Early primordial multipotent pro- genitor cells (neural stem cells) can be identified by their ability to undergo con- tinuous cellular proliferation, to regener- ate exact copies of themselves (self- renew), to generate a large number of regional cellular progeny, and to elabo- rate new cells in response to injury or dis- ease. 1 Neural progenitor cells may gener- ate different cellular species such as neurons, astrocytes, and oligodendroglia by several possible developmental mecha- nisms 10 ( Figure ). First, cytokines and other environmental cues may instruct dis- tinct early progenitor species to choose one specific neural lineage at the expense of other lineages (instructive process). Al- ternatively,additionalclassesofneuralpro- genitors may generate different lineages by probabilistic mechanisms, and only se- lected cells may survive and proliferate de-...
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