Hijacking Cellular Communications to Improve Regeneration
Researchers here spur greater regeneration following injury by broadcasting on one of the channels used for communication between cells. This is a form of cellular manipulation that will become more subtle and powerful in the years ahead as researchers gain a greater understanding of these channels and the messages they carry:
Exosomes are endosomal origin small-membrane vesicles with a size of 40 to 100 nm in diameter. They are generated by many cell types and contain functional messenger RNAs and micro RNAs (miRNAs), as well as proteins. Exosomes are well suited for small functional molecule delivery and increasing evidence indicates that they have a pivotal role in cell-to-cell communication. Recent studies indicate that exosomes and microvesicles derived from multipotent mesenchymal stromal cells (MSCs) have therapeutic promise in cardiovascular, liver, and kidney diseases. Mesenchymal stromal cells decrease neurologic deficits in rodents after stroke by increasing neurite remodeling, neurogenesis, and angiogenesis.We have previously demonstrated that functional miRNAs are transferred between MSCs and neural cells via exosomes, and that exosome-encapsulated transfer of miRNAs promotes neurite remodeling and functional recovery of stroke in rat. These data suggest that MSC-generated exosomes enhance the stroke recovery process. Thus, it is reasonable to test the hypothesis that exosomes alone when systemically administered to an animal with stroke improve functional outcome, with therapeutic benefit reflecting that observed with systemically administered MSCs. As a proof-of-principle study, we administer cell-free exosomes generated by MSCs to rats subjected to middle cerebral artery occlusion (MCAo) and investigate functional recovery as well as the mechanisms that underlie it. Our results suggest that intravenous administration of cell-free MSC-generated exosomes post stroke improves functional recovery [and] represents a novel treatment for stroke.