Human neural stem and progenitor cells: in vitro and in vivo properties, and potential for gene therapy and cell replacement in the CNS.
The generation of unlimited quantities of neural stem and/or progenitor cells derived from the human brain holds great interest for basic and applied neuroscience. In this article we critically review the origins and recent developments of procedures developed for the expansion, perpetuation, identification, and isolation of human neural precursors, as well as their attributes. Factors influencing their in vitro properties, both under division and after differentiation conditions, are evaluated, with the aim of identifying properties common to the different culture systems reported. This analysis suggests that different culture procedures result in cells with different properties, or even in different cells being isolated. With respect to in vivo performance, present evidence obtained in rodents indicate that cultured human neural precursors, in general, are endowed with excellent integrative properties. Differentiation of the implanted cells, in particular in the case of adult recipients, seems not to be complete, and functionality still needs to be demonstrated. In relation to gene transfer and therapy, aspects currently underexplored, initial data support the view that human neural stem and progenitor cells may serve a role as a platform cell for the delivery of bioactive substances to the diseased CNS. Although a large deal of basic research remains to be done, available data illustrate the enormous potential that human neural precursors isolated, expanded, and characterized in vitro hold for therapeutic applications. In spite of this potential, maintaining a critical view on many unresolved questions will surely help to drive this research field to a good end, that is, the development of real therapies for diseases of the human nervous system.
Center of Molecular Biology Severo Ochoa, Laboratory CX-450., Autonomous University of Madrid, Campus Cantoblanco, 28049-Madrid, Spain. amserrano@cbm.uam.es
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Martinez-Serrano
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Navarro
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D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000235:genetics / Q000628:therapy; D015316:Genetic Therapy; D006801:Humans; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*