The stem cells populating the white matter tracts in human brain can generate neurons, apparently just by being removed from an environment that limits them to a glial fate, according to an article in the current Nature Medicine by Steven Goldman, Neeta Roy, and their colleagues in New York City at Weill Cornell Medical College and Columbia University, and at New York Medical College in Valhalla.

Several years ago, Goldman and Roy, among others, described the presence of these glial progenitor cells (Scolding et al., 1998; Roy et al., 1999). At least a subset of these could be induced to become neurons under certain in-vitro conditions. In the current study, the authors sought to determine whether single stem cells from human white matter were capable of generating a range of neural cell types and to characterize any constraints on this process.

The researchers harvested oligodendrocyte precursor cells from tissue that had been resected from patients, primarily for epilepsy. In culture, individual precursor cells gave rise to neurospheres containing an average of 40+ cells. These undifferentiated precursors could then be induced to differentiate into neurons (capable of mature neuronal electrophysiologic function), as well as oligodendrocytes and astrocytes. At the same time, the precursors also retained the capacity to seed the formation of secondary neurospheres, whose cells also could produce all neuronal cell types. However, the white matter cells were not capable of extended replication; under the conditions of these experiments, they were limited to between 16 and 30 cell doublings.

The researchers also noted that the white matter progenitor cells did not require humorally directed "reprogramming" or exposure to basic fibroblast growth factor in order to become pluripotent, as is the case with glial progenitor cells from the rat optic nerve (Kondo and Raff, 2000) or rat forebrain. The human white matter stem cells required only the presence of PDGF and NT-3.

Finally, Goldman and colleagues took their work into an in-vivo model by grafting the human white matter progenitor cells to embryonic (E17) rat brain. When the animals were killed at four weeks of age, the descendants of the engrafted cells were found as neurons in various brain areas, including hippocampus and striatum.

"These data suggest that adult human [white matter progenitor cells] constitute a population of parenchymal glial progenitor cells whose in-situ fate is restricted by the local white-matter environment." The authors acknowledge, however, that the population may be mixed, with some cells being irreversibly committed to a glial lineage, while others retain the potential to become neurons. This question warrants further study.-Hakon Heimer.

Reference:
Nunes MC, Roy NS, Keyoung M, Goodman RR, McKhann G II, Jiang L, Kang J, Nedergaard Maiken, Goldman SA. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med. 2003 Apr;9(4):439-47. Abstract

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  1. This is a report to support neurogenesis in the adult human brain. Transplanted cells (Hoehn, 2002; Zung, 2003) and endogenous stem cells localized in the subventricular zone (Parent, 2002) are reported to migrate through white matter of the adult brain. The finding of neural progenitors in the white matter in the human brain reported in the current paper would be directly comparable to these findings in the rodent brains.

    Since the authors of this paper found limited self-renewal ability of the white matter progenitor cells (WMPCs), these cells have left the stem cell lineage and become phenotypically committed progenitors. From this point of view of limited expandability, WMPCs from the adult human brain cell may not be a good candidate for transplantable materials for neuroreplacement therapies. Moreover, starting material may also be limited because the volume of biopsy sample and the population of the cells is small.

    Rather, I think this article gives us a good rationale to treat patients with compounds that increase the progenitor cell population in the brain. Although we need more detailed stem cell population studies during aging and under disease conditions, the human adult brain may have more effective self-repair systems than we thought.

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References

Paper Citations

  1. . Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain. 1998 Dec;121 ( Pt 12):2221-8. PubMed.
  2. . Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. J Neurosci. 1999 Nov 15;19(22):9986-95. PubMed.
  3. . Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science. 2000 Sep 8;289(5485):1754-7. PubMed.
  4. . Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med. 2003 Apr;9(4):439-47. PubMed.

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Primary Papers

  1. . Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med. 2003 Apr;9(4):439-47. PubMed.