Restorative approaches in Parkinson's Disease: which cell type wins the race?

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder and is characterized by a continuous and selective loss of dopaminergic neurons in the midbrain with a subsequent reduction of the neurotransmitter dopamine in the striatum. Strategies to overcome limitations of conventional symptomatic treatment have employed cell-based strategies including transplantation of developing neural tissue or neural stem cells (NSCs) into the degenerated host brain. Still there is a tug of war for determining the ideal cell source for transplantation strategies. ES cells have the widest and most blatant potential to become the winner because they promise to be made in high quantities and to hold large amounts of the desired cell type. Adult and fetal neural stem cells have the capacity to self-renew and they are able to differentiate into all major cell-types of the brain without bearing tumorigenic potential. They can be isolated and expanded in vitro for a long time retaining the potential to differentiate into important neural cell types including dopaminergic neurons. Another source for cell-replacement are bone marrow stromal cells (MSCs). These cells can be converted into a cell type with all major features of NSCs. Efforts are made to improve these cell sources for transplantation or finding new cell sources like induced pluripotent stem cells (iPS). However, novel grounds are broken: bridging transplantations might improve the clinical outcome by restoring the nigro-striatal pathway and recruitment of endogenous stem cells by pharmacological manipulations uses the inherent regenerative potential of the diseased brain. This review discusses recent data on stem cell technology with respect to cell replacement strategies in PD as well as endogenous dopaminergic regeneration.