Abstract: |
Embryonic stem (ES) cells are characterized by their extensive self-renewal capacity and the ability to differentiate into all cell types of the embryo proper, including germ cells. The isolation of human embryonic stem (hES) cells in 1998 (Thomson et al., 1998) caused great excitement about the potential of ES cells in regenerative medicine. Cell replacement therapy in neurodegenerative disorders has been suggested as a promising application of hES therapy given the devastating nature of these diseases and the lack of alternative approaches for cellular restoration in the CNS. Parkinson's disease has emerged as a key therapeutic target for cell replacement strategies in the CNS. This is due to several Factors, such as the rather selective loss of midbrain dopamine neurons in the substantia nigra, the extensive cell death at the time of clinical manifestation, and the experiences obtained from the transplantation of fetal midbrain dopamine neurons in experimental models in animals and in human patients. This chapter will discuss the suitability of ES cells as a source for cell transplants in Parkinson's disease. After a short introduction to the basic properties and the biology of ES cells, we will describe the various strategies that have been developed to control cell fate specification in vitro, and the application of ES-derived dopamine neurons in vivo in animal models of PD. The chapter will also discuss the current state of using human and non-human primate ES cells for dopamine neuron derivation and transplantation and the potential of therapeutic cloning in Parkinson's disease. A final section will be dedicated to the problems associated with translating ES cell work to the clinic and efforts to develop therapeutic cloning as a therapeutic option in preclinical models of PD. © 2006 Springer Science+Business Media, LLC. All rights reserved. |