Cell replacement therapy for Parkinson's disease: How close are we to the clinic?

Javier Ganz, Nirit Lev, Eldad Melamed, Daniel Offen*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Cell replacement therapy (CRT) offers great promise as the future of regenerative medicine in Parkinsońs 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.

Original languageEnglish
Pages (from-to)1325-1339
Number of pages15
JournalExpert Review of Neurotherapeutics
Volume11
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Parkinson's disease
  • cell therapy
  • dopaminergic neurons
  • embryonic stem cells
  • induced pluripotent stem cells
  • mesenchymal stem cells
  • neural stem cells
  • regeneration
  • stem cells
  • transplantation

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