Mechanism of mesenchymal stem cell–induced neuron recovery and anti-inflammation |
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| Institution: | 1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA;2. Department of Pharmacology and Psychiatry, Mayo Clinic, Jacksonville, Florida, USA;3. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA;1. Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy;2. Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, City of Science and Health of Turin, Regina Margherita Children’s Hospital, Department of Public Health and Paediatrics, University of Torino, Torino, Italy;3. ALS Centre Department of Neurology, University of Eastern Piedmont, Novara, Italy;1. Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany;2. Department of Hematology, ZhongDa Hospital, Southeast University, Nanjing, P.R. China;1. Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, São Paulo State University UNESP, Botucatu, São Paulo 18618-681, Brazil;2. Proteomics Platform, Parc Cientific de Barcelona (PCB), Barcelona 08028, Spain;3. Institute for Research in Biomedicine (IRB), Barcelona 08028, Spain |
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| Abstract: | Background aimsAfter ischemic or hemorrhagic stroke, neurons in the penumbra surrounding regions of irreversible injury are vulnerable to delayed but progressive damage as a result of ischemia and hemin-induced neurotoxicity. There is no effective treatment to rescue such dying neurons. Mesenchymal stem cells (MSCs) hold promise for rescue of these damaged neurons. In this study, we evaluated the efficacy and mechanism of MSC-induced neuro-regeneration and immune modulation.MethodsOxygen-glucose deprivation (OGD) was used in our study. M17 neuronal cells were subjected to OGD stress then followed by co-culture with MSCs. Rescue effects were evaluated using proliferation and apoptosis assays. Cytokine assay and quantitative polymerase chain reaction were used to explore the underlying mechanism. Antibody and small molecule blocking experiments were also performed to further understand the mechanism.ResultsWe showed that M17 proliferation was significantly decreased and the rate of apoptosis increased after exposure to OGD. These effects could be alleviated via co-culture with MSCs. Tumor necrosis factor-α was found elevated after OGD stress and was back to normal levels after co-culture with MSCs. We believe these effects involve interleukin-6 and vascular endothelial growth factor signaling pathways.DiscussionOur studies have shown that MSCs have anti-inflammatory properties and the capacity to rescue injured neurons. |
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| Keywords: | immune modulation MSC neuro-regeneration stroke |
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