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
- Scolding N, Franklin R, Stevens S, Heldin CH, Compston A, Newcombe J. 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.
- Roy NS, Wang S, Harrison-Restelli C, Benraiss A, Fraser RA, Gravel M, Braun PE, Goldman SA. 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.
- Kondo T, Raff M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science. 2000 Sep 8;289(5485):1754-7. PubMed.
No Available Further Reading
- Nunes MC, Roy NS, Keyoung HM, Goodman RR, McKhann G, Jiang L, Kang J, Nedergaard M, 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. PubMed.