Distinguished Prof Michael Chopp studies how stem cells help the brain recover from injury

The medical use of stem cells is one of the most promising developments in modern medicine. For example, stem cells may help the brain heal following an injury. Distinguished Professor Michael Chopp, of the Department of Physics, recently published a report in the journal Stem Cells (Volume 30, Pages 1556-1564) titled Exosome-Mediated Transfer of miR-133b from Multipotent Mesenchymal Stromal Cells to Neural Cells Contributes to Neurite Outgrowth. The research team uses microRNA as a tool to study cell activity. RNA, or ribonucleic acid, acts as the intermediary between the cell’s genetic code stored in DNA and the synthesis of protein. The microRNA is unusual in that it regulates what genes are turned on and off, but does not code for a particular gene itself. The authors conclusion is that the stem cells communicate with normal brain tissue by secreting microRNA. The abstract of this paper is given below:

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.

Coauthors include Adjunct Professor Zheng Gang Zhang and Biomedical Sciences: Medical Physics graduates Ben Buller and Mark Katakowski. The research is performed at Henry Ford Hospital in Detroit, Michigan, and is supported by grants from the National Institutes of Health.