Figure 1.

Phenotype of hGRPs transplanted into myelin-deficient, immunodeficient mouse brain. (A–C) Two weeks after ICV transplantation, HuNA-positive hGRPs were found within or near the vicinity of the lateral ventricle. Occasionally, grafted cells co-localized with the Olig2 marker (A) or GFAP (B). MBP expression at this time was not detected (C). (D–F) Six weeks after transplantation, hGRPs substantially expand and were found in brain structures relatively close to the ventricles. A large proportion of the cells expressed Olig2 (D) and some of those residing within gray matter were positive for GFAP (E, arrowhead). At this time, the first MBP-positive oligodendrocytes could be observed (F). (G–I) Thirteen weeks after grafting, many hGRPs co-express the Olig2 marker (G), with those positive for GFAP presenting a more mature astroglial morphology (H). At this point, MBP expression and myelination in some brain structures was very robust (I) High resolution confocal microscopy (I, inset) demonstrates that MBP myelin (red) surrounds TuJ1 axons (green). (J–M) electron microscopy 14 weeks after cell transplantation revealed that many axons within corpus callosum were surrounded by thick myelin sheaths (J). High magnification images clearly demonstrate a normal myelin structure with multiple layers of compact myelin and dense lines present (K). Numerous axons exhibited a myelin structure typical for the shiverer phenotype with only a few loosely organized lamellae (L,M).