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The subcortical white matter of the adult human brain harbors a pool of glial progenitor cells. These cells can be isolated by fluorescence-activated cell sorting (FACS) after either transfection with green fluorescent protein (GFP) under the control of the CNP2 promoter, or A2B5-targeted immunotagging. Although these cells give rise largely to oligodendrocytes, in low-density culture we observed that some also generated neurons. We thus asked whether these nominally glial progenitors might include multipotential progenitor cells capable of neurogenesis. We found that adult human white-matter progenitor cells (WMPCs) could be passaged as neurospheres in vitro and that these cells generated functionally competent neurons and glia both in vitro and after xenograft to the fetal rat brain. WMPCs were able to produce neurons after their initial isolation and did not require in vitro expansion or reprogramming to do so. These experiments indicate that an abundant pool of mitotically competent neurogenic progenitor cells resides in the adult human white matter., Author(s): Marta C. Nunes [1, 4]; Neeta Singh Roy [1, 4]; H. Michael Keyoung [1]; Robert R. Goodman [2]; Guy McKhann, II [2]; Li Jiang [3]; Jian Kang [3]; Maiken [...]

Lineage-restricted progenitors of the central nervous system (CNS) are not readily expandable because their mitotic competence is limited. Here we used retroviral overexpression of human telomerase reverse transcriptase (hTERT) to immortalize progenitors from human fetal spinal cord. The hTERT-immortalized cells divided in basic fibroblast growth factor (bFGF) expressed high telomerase activity, and gave rise to phenotypically restricted subpopulations of either glia or neurons. The latter included a prototypic line, hSC11V-TERT, that gave rise only to neurons. These included both chx10+ interneurons and Islet1+/Hb9+/ChAT+ motor neurons; the latter were recognized by green fluorescent protein (GFP) driven by the Hb9 enhancer. The neurons were postmitotic and achieved electrophysiologic competence. Upon xenograft to both fetal rat brain and injured adult spinal cord, they matured as neurons and survived for 6 months, with no evident tumorigenesis. The cells have survived >168 doublings in vitro, with karyotypic normalcy and without replicative senescence. hTERT overexpression thus permits the generation of progenitor lines able to give rise to phenotypically restricted neurons. [ABSTRACT FROM AUTHOR]

Neural precursor cells are dispersed widely throughout the adult brain. A population of multipotential progenitor cells, capable of giving rise to both neurons and glia, lines the cerebral ventricles of all adult animals, including humans. In addition, glial progenitor cells, which also have the capacity to generate multiple cell types, are dispersed throughout the subcortical white matter and cortex. Each of these categories of progenitor cells exists in, and has been isolated from, the adult human brain. We have begun to ask how these cells might be used therapeutically. We report here examples of two potential strategies for their use: (1) transplantation of phenotypically restricted progenitors, in which purified isolates of defined human precursor cells are implanted into disease sites, and (2) induction in vivo, in which resident progenitor cells are stimulated by delivered growth factors. We find that each of these strategies has potential therapeutic efficacy, and discuss the most likely and feasible clinical targets for their clinical application. [Copyright &y& Elsevier]