Cell replacement therapy for Parkinson''s disease: how close are we to the clinic?. (September 2011)

• Record Type: Journal Article
• Authors: Ganz, Javier; Lev, Nirit; Melamed, Eldad; Offen, Daniel
• Is Part Of: Expert review of neurotherapeutics. Volume 11:Number 9(2011)
• Page Start: 1325
• Page End: 1339
• Publication Date: 2011-09
• Subjects: cell therapy -- dopaminergic neurons -- embryonic stem cells -- induced pluripotent stem cells -- mesenchymal stem cells -- neural stem cells -- Parkinson''s disease -- regeneration -- stem cells -- transplantation; Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1586/ern.11.74
• Languages: English
• ISSNs: 1473-7175

Abstract

Cell replacement therapy (CRT) offers great promise as the future of regenerative medicine in Parkinson´s disease (PD). Three decades of experiments have accumulated a wealth of knowledge regarding the replacement of dying neurons by new and healthy dopaminergic neurons transplanted into the brains of animal models and affected patients. The first clinical trials provided the proof of principle for CRT in PD. In these experiments, intrastriatal transplantation of human embryonic mesencephalic tissue reinnervated the striatum, restored dopamine levels and showed motor improvements. Sequential controlled studies highlighted several problems that should be addressed prior to the wide application of CRT for PD patients. Moreover, owing to ethical and practical problems, embryonic stem cells require replacement by better-suited stem cells. Several obstacles remain to be surpassed, including identifying the best source of stem cells for A9 dopaminergic neuron generation, eliminating the risk of tumor formation and the development of graft-induced dyskinesias, and standardizing dopaminergic cell production in order to enable clinical application. In this article, we present an update on CRT for PD, reviewing the research milestones, various stem cells used and tailored differentiation methods, and analyze the information gained from the clinical trials.