Cell replacement therapy for Parkinson’s disease: how close are we to the clinic?

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.

Keywords::

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

Financial & competing interests disclosure

This work was performed in partial fulfillment of the requirements for a PhD degree for Javier Ganz. This work was supported by the Devora Eleonora Kirshman Fund for research of Parkinson’s Disease, Tel Aviv University (Eldad Melamed), by the Norma and Alan Aufzein chair of research of Parkinson’s Disease (Eldad Melamed) and the Israeli Science Foundation (ISF; Nirit Lev). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.