Prospects of stem cell therapy for replacing dopamine neurons in Parkinson's disease.
In Parkinson's disease (PD), the main pathology is a loss of nigrostriatal dopamine (DA) neurons. Clinical trials with intrastriatal transplantation of human embryonic mesencephalic tissue have shown that grafted DA neurons reinnervate the striatum, restore striatal DA release and, in some patients, induce major clinical benefit. Stem cells could provide an unlimited source of DA neurons for transplantation. Recent studies demonstrate that cells with properties of mesencephalic DA neurons can be produced from stem cells of different sources including reprogrammed somatic cells. However, as we discuss here, it remains to be shown that these cells can provide efficient functional reinnervation and behavioral recovery in animal PD models. Moreover, a clinically competitive cell therapy for PD will require better criteria for patient selection, improved functional efficacy of grafts by a tailor-made transplantation procedure providing optimum repair of the patient's DA system and strategies to prevent dyskinesias and tumor formation.
Lindvall
Olle
O
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden. olle.lindvall@med.lu.se
Kokaia
Zaal
Z
D000818:Animals; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D004298:Dopamine / Q000172:deficiency / Q000502:physiology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D009474:Neurons / Q000473:pathology / Q000637:transplantation*; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection
D004298:Dopamine