In vitro differentiation of transplantable neural precursors from human embryonic stem cells

The remarkable developmental potential and replicative capacity of human em bryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differe ntiation, enrichment, and transplantation of neural precursor cells from hu man ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fib roblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differe ntiated into neurons, astrocytes, and oligodendrocytes. After transplantati on into the neonatal mouse brain human ES cell-derived neural precursors we re incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.