PMID- 24927715 OWN - NLM STAT- MEDLINE DCOM- 20151207 LR - 20181202 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 16 IP - 10 DP - 2014 Oct TI - Mechanism of mesenchymal stem cell-induced neuron recovery and anti-inflammation. PG - 1336-44 LID - S1465-3249(14)00605-7 [pii] LID - 10.1016/j.jcyt.2014.05.007 [doi] AB - BACKGROUND AIMS: After 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. METHODS: Oxygen-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. RESULTS: We 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-alpha 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. DISCUSSION: Our studies have shown that MSCs have anti-inflammatory properties and the capacity to rescue injured neurons. CI - Copyright (c) 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Huang, Peng AU - Huang P AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Gebhart, Nichole AU - Gebhart N AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Richelson, Elliott AU - Richelson E AD - Department of Pharmacology and Psychiatry, Mayo Clinic, Jacksonville, Florida, USA. FAU - Brott, Thomas G AU - Brott TG AD - Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Meschia, James F AU - Meschia JF AD - Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA. FAU - Zubair, Abba C AU - Zubair AC AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA. Electronic address: Zubair.Abba@Mayo.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140611 PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Apoptosis/physiology MH - *Cell Communication MH - Cell Hypoxia/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Glucose/deficiency/metabolism MH - Humans MH - Inflammation/metabolism/pathology/*prevention & control MH - Interleukin-6/metabolism/pharmacology MH - Mesenchymal Stem Cells/metabolism/*physiology MH - Neuritis/metabolism/*prevention & control MH - Neurons/drug effects/pathology/*physiology MH - Stroke/pathology/*therapy MH - Tumor Necrosis Factor-alpha/metabolism MH - Vascular Endothelial Growth Factor A/metabolism/pharmacology OTO - NOTNLM OT - MSC OT - immune modulation OT - neuro-regeneration OT - stroke EDAT- 2014/06/15 06:00 MHDA- 2015/12/15 06:00 CRDT- 2014/06/15 06:00 PHST- 2014/01/10 00:00 [received] PHST- 2014/04/05 00:00 [revised] PHST- 2014/05/02 00:00 [accepted] PHST- 2014/06/15 06:00 [entrez] PHST- 2014/06/15 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S1465-3249(14)00605-7 [pii] AID - 10.1016/j.jcyt.2014.05.007 [doi] PST - ppublish SO - Cytotherapy. 2014 Oct;16(10):1336-44. doi: 10.1016/j.jcyt.2014.05.007. Epub 2014 Jun 11.