[Frontiers in Bioscience S3, 1407-1420, June 1, 2011]

Neuroinflammation and cell therapy for Parkinson's disease

Feng Li1, Shaowei Zhu2, Chengyuan Wu1, Chuanzhu Yan2, Yuguang Liu1 Shugan Zhu1

1Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, P. R. China 2Department of Neurosurgery Neurology, Qilu Hospital of Shandong University, Jinan, 250012, P. R. China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Neuroinflammation in PD 3.1. Microglial activation in PD
3.2. Cytotoxic effects of activated microglia in PD
3.3. Reactive microgliosis and sustained, chronic inflammation in PD 4. Neuroinflammation modulates the fate of grafted cells 4.1. Role of inflammation on cell survival and stem cell proliferation
4.2. Role of inflammation on stem cell migration and homing
4.3. Role of inflammation on stem cell differentiation and integration
5. Graft rejection and allogeneic/xenogeneic stem cells
6. Immunomodulatory effects of stem cells
7. Conclusions and perspectives
8. Acknowledgements
9. References

1. ABSTRACT

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.