In spite of increasing numbers of publications about cell replacement therapies in various neurodegenerative
diseases, reports on therapeutic benefits are still rare due to the huge array of parameters affecting the clinically relevant
outcome. Limiting conditions can be attributed to origin and number of cells used for transplantation, their in vitro storage,
propagation and/or predifferentiation. In addition, the ability of these cells for a site directed differentiation and functional
integration in sufficient numbers is known to depend on extrinsic factors including intracerebral position of graft(s).
Thus, obstacles to the use of cells in replacement therapies of neurological disorders reflect the molecular as well as cellular
complexity of affected functional systems. This review will highlight central aspects of cell replacement strategies that
are currently regarded as the most limiting issues in respect to survival, cell identity and site directed differentiation as
well as functional integration of grafts. Special attention will be paid to neural stem cells, derived from either fetal or adult
central nervous tissue. Unravelling the molecular biology of these proliferating cells in combination with instructive environmental
cues for their site directed differentiation will pave the way to high reproducibility in collection, propagation,
and predifferentiation of transplantable cells in vitro. In addition, this knowledge of intrinsic and extrinsic cues for a site
directed neural differentiation during development will broaden the perspective for any pluripotent stem cell, namely embryonic
stem and induced pluripotent stem cells, as an alternate source for a cell based therapy of neurodegenerative diseases.