Current Developments in Cell Replacement Therapy for Parkinson's Disease

Parkinson's disease (PD) is characterized by tremor, rigidity, and bradykinesia. PD is caused mainly by depletion of the nigrostriatal pathway. Conventional medications such as levodopa are highly effective in the early stage of PD; however, these medications fail to prevent the underlying neurodegeneration. Cell replacement therapy (CRT) is a strategy to achieve long-term motor improvements by preventing or slowing disease progression. Replacement therapy can also increase the number of surviving dopaminergic neurons, an outcome confirmed by positron emission tomography and immunostaining. Several promising cell sources offer authentic and functional dopaminergic replacement neurons. These cell sources include fetal ventral mesencephalic tissue, embryonic stem cells (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs) from various tissues, induced pluripotent stem cells (iPSCs), and induced neural cells. To fully develop the potential of CRT, we need to recognize the advantages and limitations of these cell sources. For example, although fetal ventral midbrain is efficacious in some patients, its ethical issues and the existence of graft-induced dyskinesias (GID) have prevented its use in large-scale clinical applications. ESCs have reliable isolation protocols and the potential to differentiate into dopaminergic progenitors. iPSCs and induced neural cells are suitable for autologous grafting. Here we review milestone improvements and emerging sources for cell-based PD therapy to serve as a framework for clinicians and a key reference to develop replacement therapy for other neurological disorders.