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

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.

A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases.

Biofunctional matrices for in vivo tissue engineering strategies must be modifiable in both biomolecular composition and mechanical characteristics. To address this challenge, we present a modular system of biohybrid hydrogels based on covalently cross-linked heparin and star-shaped poly(ethylene glycols) (star-PEG) in which network characteristics can be gradually varied while heparin contents remain constant. Mesh size, swelling and elastic moduli were shown to correlate well with the degree of gel component cross-linking. Additionally, secondary conversion of heparin within the biohybrid gels allowed the covalent attachment of cell adhesion mediating RGD peptides and the non-covalent binding of soluble mitogens such as FGF-2. We applied the biohybrid gels to demonstrate the impact of mechanical and biomolecular cues on primary nerve cells and neural stem cells. The results demonstrate the cell type-specific interplay of synergistic signaling events and the potential of biohybrid materials to selectively stimulate cell fate decisions. These findings suggest important future uses for this material in cell replacement based-therapies for neurodegenerative diseases.