A research study has demonstrated the neuroprotective effect of mesenchymal stem cells (MSCs) in clearing extracellular α-synuclein in patients with multiple system atrophy (MSA). The study proposes the use of MSCs as a disease-modifying therapy for patients with α-synucleinopathies.
α-Synuclein aggregates are prion-like particles comprising of monomeric, oligomeric or fibrillar forms and are involved in the pathogenesis of a-synucleinopathies, such as Parkinson’s disease, MSA and dementia.
In the present study published in Acta Neuropathologica, Dr. Phil Hyu Lee and team (Yonsei University College of Medicine, South Korea) investigated whether MSCs could exert neuroprotective effects in α-synuclein-enriched mice models and patients with MSA. In vitro experiments performed in BV2 microglial cells showed that treatment of these cells with α-synuclein induced an inflammatory phenotype, whereas co-culture of α-synuclein-treated BV2 cells with MSCs showed a reduction in α-synuclein levels and induced an anti-inflammatory phenotype. The co-cultured cells also showed an increase in lysosomal activity and displayed greater viability of neuronal cells.
Using siRNAs and knockout mice models, the team discovered that IL-4 secreted from MSCs induced phagocytic clearance of α-synuclein through M2 microglia polarization. In α-synuclein-injected mice, MSC treatment induced M2 microglia polarization, decreased α-synuclein levels and enhanced neuronal survival. Cerebrospinal fluid (CSF) from MSC-transplanted MSA patients induced microglia M2 polarization in α-synuclein-treated BV2 cells. More interestingly, CSF analysis from baseline to 1-year follow-up demonstrated that α-synuclein clearance was greater in the CSF of MSC-transplanted MSA patients than in placebo-transplanted patients.
Thus, the study indicate that MSCs exert a neuroprotective effect via the clearance of extracellular α-synuclein by controlling microglia M2 polarization. This property of MSCs in modulating the clearance of extracellular a-synuclein could be applicable to future clinical strategies for treatment of patients with a-synucleinopathies.
Source: Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder. Park HJ et al., Acta Neuropathologica August 2016. DOI