Clinical application of stem cell therapy in Parkinson's disease.
Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce long-lasting symptomatic relief without side effects while counteracting PD progression.
Centre for Neuroscience, Department of Medicine, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0NN, UK. marios.politis@imperial.ac.uk
Marios
M
Politis
Olle
O
Lindvall
D053687:Adult Stem Cells / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002986:Clinical Trials as Topic; D003342:Corpus Striatum / Q000473:pathology / Q000601:surgery; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000473:pathology / Q000502:physiology*; D006801:Humans; D058953:Neural Stem Cells / Q000637:transplantation*; D055495:Neurogenesis; D010300:Parkinson Disease / Q000473:pathology / Q000601:surgery*; D020127:Recovery of Function; D033581:Stem Cell Transplantation
D004298:Dopamine