Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury
Figure 7
Transplanted SNS, but not PNS, promoted axonal growth, remyelination and functional recovery.
(A) NF-H-positive neuronal fibers were observed along with GFAP-positive immature astrocytes derived either from the Venus-positive grafts or the host, and crossed the perilesional area in the SNS group. Scale bar: 50 µm. (B) Higher magnification images of the boxed area in A. Arrows: some examples of axons associated with Venus (GFP)-positive astrocytes. (C) Immunohistochemical analysis of MBP and NF-H in the SNS-transplanted injured spinal cord. SNS-derived Venus-positive cells differentiated into MBP-positive oligodendrocytes, which myelinated NF-H-positive fibers. Scale bar: 20 µm. (D)(E)(F) Representative electron-microscopic images of a remyelination site in sagittal sections from injured spinal cords grafted with SNS, which were immunostained for Venus (grafted cells) using an anti-GFP antibody. Low-magnification images show a group of grafted cells with active remyelination (some indicated by open arrowheads) (D). High-magnification images from (E-1) to (E-12) were obtained from (D), and show various numbers of lamellae in the myelin sheath. The remyelinating transplanted cells were detected as black dots (arrowheads). Venus (GFP)-positive dots (arrows) were localized to the outer and inner mesaxons of the myelin cytoplasm (OM, IM) (F). My: Myelination, N: Nucleus, Scale bar: 5 µm for D, 200 nm for E and F. (G) Mean Basso Mouse Scale for Locomotion (BMS) scores for each group over the 49-day recovery period. Although there was no significant difference in the BMS scores among the control, PNS, and SNS groups on day 14, the SNS group exhibited significantly better functional recovery than the PNS and control groups on day 21 and thereafter. On the other hand, there was no significant difference in the BMS scores between the PNS and control groups. Values are means ± s.e.m. (n = 11), *: P<0.05, SNS vs. control, 42 days after injury. **: SNS vs. PNS or SNS vs. control on day 21, 28, 35, and 49 after injury.