Differentiation and histological analysis of embryonic stem cell-derived neural transplants in mice

We report here that neural transplantation of in vitro-differentiated embry onic stem (ES) cells provides a versatile strategy for gene transfer into t he central nervous system. ES cells were subjected to an optimized in vitro differentiation protocol to obtain embryoid bodies. These aggregates were stereotaxically transplanted into the brain of recipient adult mice, where they followed a strictly controlled differentiation pattern and eventually formed mature neural grafts. A marker gene, introduced into the ROSA26 locu s allowed for precise determination of the fate of the descendants of the t ransplanted embryoid bodies and revealed that not only neurons but also ast rocytes, oligodendrocytes and even microglial cells were graft-derived. Eva luation of long-term experiments showed viable grafts with a stable transge ne expression and proved that this approach provides a tool for reliable ge ne expression within a spatially delimited area of neural tissue.