Neuroinflammation and cell therapy for Parkinson's disease.
Cell therapy is a promising therapeutic alternative for Parkinson's disease, and one possible limiting factor may be that the pathological environment of PD is hostile for the process of neurogenesis, including grafted stem cells survival, proliferation, migration and dopaminergic neuronal fate specification along with maturation of the immature neurons and ultimately integration of the new neuronal progeny into functional neuronal circuits. Uncontrolled microglial activation and neuroinflammation contributes to neuronal damage in PD. Similarly, the microglia-derived inflammatory mediators may also influence grafted stem cells. Thus, we discuss reactive microgliosis and sustained, chronic neuroinflammation in PD, together with cytokine-dependent neurotoxicity and inflammation-derived oxidative stress on dopaminergic neuron in the substantia nigra pars compacta substantia nigra pars compacta (SNpc). Based on these, we further summarize the interaction between neuroinflammation and stem cells, and conclude that neuroinflammation acts as double-edged swords, instead of simply beneficial or detrimental, and stem cells display immunomodulatory functions beneficial for dopaminergic neurons via an anti-inflammatory action in PD.