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Tissue-Specific Stem Cells
Version of Record online: 18 JUN 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 7, pages 1556–1564, July 2012
How to Cite
Xin, H., Li, Y., Buller, B., Katakowski, M., Zhang, Y., Wang, X., Shang, X., Zhang, Z. G. and Chopp, M. (2012), Exosome-Mediated Transfer of miR-133b from Multipotent Mesenchymal Stromal Cells to Neural Cells Contributes to Neurite Outgrowth. STEM CELLS, 30: 1556–1564. doi: 10.1002/stem.1129
Author contributions: H.X.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; Y.L.: conception and design, data analysis and interpretation, financial support, and manuscript writing; B.B., M.K., Y.Z., X.W., and X.S.: collection and/or assembly of data; Z.G.Z.: conception and design, data analysis and interpretation, and financial support; M.C.: conception and design, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS May 17, 2012.
- Issue online: 18 JUN 2012
- Version of Record online: 18 JUN 2012
- Accepted manuscript online: 17 MAY 2012 03:36PM EST
- Manuscript Accepted: 30 APR 2012
- Manuscript Received: 5 JAN 2012
- NINDS. Grant Numbers: R01 AG037506, R01 NS66041, R01 NS75156
- MicroRNA 133b;
- Multipotent mesenchymal stromal cells;
- Neurite outgrowth;
Multipotent mesenchymal stromal cells (MSCs) have potential therapeutic benefit for the treatment of neurological diseases and injury. MSCs interact with and alter brain parenchymal cells by direct cell-cell communication and/or by indirect secretion of factors and thereby promote functional recovery. In this study, we found that MSC treatment of rats subjected to middle cerebral artery occlusion (MCAo) significantly increased microRNA 133b (miR-133b) level in the ipsilateral hemisphere. In vitro, miR-133b levels in MSCs and in their exosomes increased after MSCs were exposed to ipsilateral ischemic tissue extracts from rats subjected to MCAo. miR-133b levels were also increased in primary cultured neurons and astrocytes treated with the exosome-enriched fractions released from these MSCs. Knockdown of miR-133b in MSCs confirmed that the increased miR-133b level in astrocytes is attributed to their transfer from MSCs. Further verification of this exosome-mediated intercellular communication was performed using a cel-miR-67 luciferase reporter system and an MSC-astrocyte coculture model. Cel-miR-67 in MSCs was transferred to astrocytes via exosomes between 50 and 100 nm in diameter. Our data suggest that the cel-miR-67 released from MSCs was primarily contained in exosomes. A gap junction intercellular communication inhibitor arrested the exosomal microRNA communication by inhibiting exosome release. Cultured neurons treated with exosome-enriched fractions from MSCs exposed to 72 hours post-MCAo brain extracts significantly increased the neurite branch number and total neurite length. This study provides the first demonstration that MSCs communicate with brain parenchymal cells and may regulate neurite outgrowth by transfer of miR-133b to neural cells via exosomes. STEM CELLS2012;30:1556–1564