Exosome-Mediated Transfer of miR-133b from Multipotent Mesenchymal Stromal Cells to Neural Cells Contributes to Neurite Outgrowth
By Hongqi Xin, Yi Li, Benjamin Buller, M. Katakowski, Yi Zhang, Xinli Wang, Xia Shang, Zhenggang Zhang, Michael Chopp. Stem Cells, 2012
830 citations recorded by the source corpus.
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
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/338b33ff7c045e3b571128ebcaa1405d0e1a723c
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Citations in the corpus
- Mechanisms of mesenchymal stem/stromal cell function (2016, background): “and recovery by virtue of transfer of miR-133b [170, 171].”
- Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. (2015, background): “Exosome-mediated transfer of miR-133b from MSCs to neural cells stimulated neurite growth (104).”
- Exosomes Derived from Mesenchymal Stem Cells (2014, background): “This experiment provides the first evidence that MSCs communicate with brain parenchymal cells via exosome-mediated miR-133b transfer, leading to regulation of specific gene expression that enhances neurite outgrowth and functional recovery [53].”
- Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth (2013, background): “Cultured MSCs release significant amounts of exosomes which contain functional miRNAs [23].”