Treatment of Parkinson's disease using cell transplantation

Abstract

The clinical trials with intrastriatal transplantation of human fetal mesencephalic tissue, rich in dopaminergic neurons, in Parkinson's disease (PD) patients show that cell replacement can work and in some cases induce major, long-lasting improvement. However, owing to poor tissue availability, this approach can only be applied in very few patients, and standardization is difficult, leading to wide variation in functional outcome. Stem cells and reprogrammed cells could potentially be used to produce dopaminergic neurons for transplantation. Importantly, dopaminergic neurons of the correct substantia nigra phenotype can now be generated from human embryonic stem cells in large numbers and standardized preparations, and will soon be ready for application in patients. Also, human induced pluripotent stem cell-derived dopaminergic neurons are being considered for clinical translation. Available data justify moving forward in a responsible way with these dopaminergic neurons, which should be tested, using optimal patient selection, cell preparation and transplantation procedures, in controlled clinical studies.

Keywords: Parkinson's disease; dopaminergic neurons; neural grafts; reprogramming; stem cells; transplantation.

© 2015 The Author(s).

Figures

Figure 1.

Schematic of potential sources of dopaminergic neurons for transplantation in PD patients. (i) Human fetal mesencephalic tissue, rich in dopaminergic neuroblasts, made into a cell suspension; (ii) neural stem/progenitor cells from human fetal mesencephalon, expanded and differentiated to dopaminergic neuroblasts; (iii) pluripotent cells generated from human blastocysts (ES cells) or fibroblasts (iPS cells), expanded and differentiated to dopaminergic neuron precursors/neuroblasts; (iv) human fibroblasts directly converted to dopaminergic neuron precursors/neuroblasts. The dopaminergic cells are implanted stereotaxically into the striatum, primarily putamen.