Transplanted Adult Neural Stem Cells Express Sonic Hedgehog In Vivo and Suppress White Matter Neuroinflammation after Experimental Traumatic Brain Injury

Figure 7

Induced genetic in vivo labeling of host cells expressing Gli1 in the subventricular zone (SVZ) following brain injury and human non-NSC transplantation. (a) Experimental time line for human HEK transplantation into Gli1^CreERT2;R26YFP host mice. The HEK293 cells expressing the tdTomato reporter (HEK-Tom cells) were transplanted into the lateral ventricle (LV) 2 weeks after craniotomy and the controlled cortical impact (CCI) model of TBI to produce cortical tissue damage. (b) Immunohistochemistry for the pan T-lymphocyte cell (T-cell) marker CD3 shows T-lymphocytes infiltrate regions surrounding the human HEK293 cells as early as 1 week following transplantation into a sham mouse. (c–h) Coronal sections from injured mice were immunostained with either GFAP (astrocytes, green), CD11b (macrophages, green), or CD3 (T-cells, green) to analyze the host immune response at 2 weeks postinjection. Immunolabeling for GFAP (c, f), CD11b (d, g), and CD3 (e, h) shows a localized immune response to HEK-Tom cells in the LV (f–h) that is not observed with vehicle injection (c–e). (i-j) Genetic in vivo labeling of host cells with YFP (green) indicates Gli1 expression after HEK-Tom transplantation. Gli1-YFP labeling is increased in the ipsilateral SVZ adjacent to HEK-Tom cells (i) compared to the contralateral side (j). All sections were counterstained with DAPI (blue) nuclear stain. Scale bar = 200 μm (c), (d), 100 μm (i). Representative images are shown from analysis of sham + HEK-Tom (), CCI + vehicle (), CCI + HEK-Tom ().