Fig. 2.

Glial progenitor cell graft-mediated myelination of a dysmyelinated host. (A) A 13-month-old shiverer (shi/shi) × rag2^−/− mouse, neonatally xenografted with A2B5⁺/PSA-NCAM⁻ hGPCs. MBP, myelin basic protein (shown in green). Shiverer mice do not express MBP; all immunolabeled myelin is of donor origin. (B) Sagittal view through the cerebellum. All cells were stained with 4′,6-diamidino-2-phenylindole (blue); donor cells were identified by human nuclear antigen (hN, red) and MBP (green). (C) Kaplan-Meier plot comparing survival of neonatally engrafted shiverer × rag2^−/− mice to untreated and saline-injected controls. (D) CD140a-selected GPCs transplanted into neonatal shiverer × rag2^−/− mice expanded and migrated extensively, rendering the brains chimeric. Red dots indicate individual human cells (hN); sacrificed at 3 months. (E and F) Coronal sections of a neonatally engrafted shiverer brain at 3 months, revealing donor-derived myelination (MBP, red) and astrocytic infiltration [human glial fibrillary acidic protein (GFAP), green] of the corpus callosum. (G) Myelin (MBP, red) produced by CD140a-selected hGPCs ensheathes mouse neurofilament-positive axons (NF, green), at 3 months. (H) Reconstituted nodes of Ranvier in the cervical spinal cord of a transplanted and rescued 1-year-old shiverer × rag2^−/− mouse, showing paranodal Caspr protein and juxtaparanodal voltage-gated potassium channel protein Kv1.2, symmetrically flanking each axonal node. Untransplanted shiverer brains do not have organized nodes of Ranvier and, hence, cannot support saltatory conduction by central axons (Caspr, red; Kv1.2, green). Scale bars: (A) and (B), 1 mm; (E), 50 μm; (F) and (G), 10 μm; (H), 5 μm. (A) and (B), from (54); (C) and (H), from (5); (D) to (G), from (10).