Exosome-Mediated Transfer of miR-133b from Multipotent Mesenchymal Stromal Cells to Neural Cells Contributes to Neurite Outgrowth
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Open Access
- 18 June 2012
- journal article
- tissue specific-stem-cells
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 30 (7), 1556-1564
- https://doi.org/10.1002/stem.1129
Abstract
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.Keywords
Funding Information
- NINDS (R01 AG037506, R01 NS66041, R01 NS75156)
This publication has 83 references indexed in Scilit:
- IGF-II is regulated by microRNA-125b in skeletal myogenesisThe Journal of cell biology, 2011
- Exosomes: Extracellular organelles important in intercellular communicationJournal of Proteomics, 2010
- Export of microRNAs and microRNA-protective protein by mammalian cellsNucleic Acids Research, 2010
- Functional delivery of viral miRNAs via exosomesProceedings of the National Academy of Sciences of the United States of America, 2010
- Bone Marrow Stromal Cells Enhance Inter- and Intracortical Axonal Connections after Ischemic Stroke in Adult RatsJournal of Cerebral Blood Flow & Metabolism, 2010
- Mesenchymal Stem Cell: Present Challenges and Prospective Cellular Cardiomyoplasty Approaches for Myocardial RegenerationAntioxidants and Redox Signaling, 2009
- Marrow stromal cell transplantation in stroke and traumatic brain injuryNeuroscience Letters, 2009
- Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cellsNature, 2007
- MicroRNA-133 controls cardiac hypertrophyNature Medicine, 2007
- MicroRNAs and their regulatory roles in animals and plantsJournal of Cellular Physiology, 2006