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Stem cells derived from various tissues are emerging as an ethically less controversial and technically more controllable alternative source to fetal primary cells for transplantation in Parkinson’s disease (PD), for replacing degenerating endogenous dopaminergic neurons in the substantia nigra. There is a reasonable hope that stem cell transplantation can become a clinically relevant alternative treatment strategy not only for PD but also for other neurodegenerative diseases. However, our knowledge on how transplanted stem‐cell‐derived dopaminergic neurons integrate into the host tissue is relatively limited. In this chapter we discuss various aspects of stem cell therapy that need to be explored in depth to be able to understand the mechanisms of their therapeutic action. In particular, to what extent grafted stem cells need to attain neuronal properties, and synaptically integrate into the host neuronal circuitry to achieve functional recovery of the Parkinsonian brain.

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