Behavioral improvement after transplantation of neural precursors derived from embryonic stem cells into the globally ischemic brain of adolescent rats

Abstract

We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats. Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2 weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods. From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals. Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats.