TREM2-Transduced Myeloid Precursors Mediate Nervous Tissue Debris Clearance and Facilitate Recovery in an Animal Model of Multiple Sclerosis (original) (raw)
Figure 7
Application of TREM2-Transduced Myeloid Cells Reduced Axonal and Myelin Injury
(A) Reduced spinal cord axonal injury and decreased demyelination after cell therapy by TREM2-transduced myeloid cells. Axonal injury and damage were analyzed by immunostaining with specific antibodies directed against APP and dephosphorylated neurofilament (SMI32) at day 14 after cell application. Demyelination was determined by LFB staining at day 14 after cell application. Mice were injected at day 4 after first clinical signs of EAE by TREM2-transduced myeloid precursor cells (TREM2-BM-MC), GFP-transduced BM-MC (GFP-BM-MC), or PBS control. Representative histological pictures are shown. Scale bars for APP and LFB indicate 200 μm, and for inserts indicate 50 μm. Scale bar for SMI32 indicates 50 μm, and for insert indicates 20 μm.
(B) Quantification of axonal damage and demyelination 14 d after cell application in EAE with TREM2-transduced myeloid cells (black bars), control GFP vector–transduced myeloid cells (green bars), or vehicle PBS control (red bars). Level of axonal injury (APP-positive deposits/mm2), axonal damage (relative number of SMI32-positive axons), and demyelination (loss of LFB, as a percentage) were significantly reduced after cell therapy with TREM2-transduced BM-MC. For quantitative analysis, at least three lumbar spinal cord sections of three mice per group were investigated. Data are presented as mean ± SEM. ANOVA followed by unpaired _t_-test: p = 0.0425 (TREM2 versus GFP) and p = 0.0759 (TREM2 versus PBS) in APP; p = 0.0012 (TREM2 versus GFP) and p = 0.0098 (TREM2 versus PBS) in SMI32; p = 0.0465 (TREM2 versus GFP) and p = 0.00450 (TREM2 versus PBS) in LFB.