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Home: Papers of the Week
Annotation


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 Abstract


Corresponding Author: Steven Goldman
  
Comments on Paper and Primary News
  Primary News: Breaking Away: Human Glial Stem Cells Generate Neurons

Comment by:  Kiminobu Sugaya
Submitted 19 March 2003  |  Permalink Posted 19 March 2003

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....  Read more

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REAGENTS/MATERIAL:
Xenografted rat brains sections were immunostained with III-tubulin–specific antibody TuJ1 (1:600; Covance), MAP2-specific antibody AP-20 (1:50; Sigma), HuC/HuD-specific mouse monoclonal antibody 16A11 (25 g/ml; H. Furneaux, Memorial Sloan-Kettering Cancer Center, New York), GAD67-specific rabbit antibody (1:100; Chemicon), GFAP-specific mouse antibody SMI 21 (1:1,000; Sternberger), GFAP-specific rabbit antibody (1:400; Sigma), CNP-specific mouse antibody SMI 91 (1:1000 Sternberger), human nestin–specific rabbit antibody (1:200; Chemicon), or doublecortin-specific rabbit antisera (1:100; C. Walsh, Harvard Medical School, Boston, Massachusetts). For multiple-antigen labeling, antibodies against III-tubulin, MAP-2, GFAP and BrdU (BrdU-specific rat antibody; 1:200; Harlan, now carried by Immunologicals Direct) were incubated overnight at 4 °C. Fixed cultures were counterstained with DAPI (10 g/ml; Molecular Probes).

FUTURE DIRECTION:
As outlined by Kimonobu Sugaya in his comment, the stem cells isolated from the white matter are limited in their ability to double, suggesting that they may be of limited use for transplantation studies. However, the results are consistent with white matter neurogenesis and it would be interesting to determine if the such neurons are functional.

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