Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats

Abstract Background Although exosomes, as byproducts of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal injury (SCI), their mechanism action remains unclear. Methods We designed and performed this study determine whether exosomes attenuate the lesion size SCI by ameliorating neuronal induced a secondary inflammatory storm promoting neurite outgrowth. determined absolute levels all exosomal miRNAs investigated potential mechanisms miR-199a-3p/145-5p in inducing outgrowth vivo vitro. Results miR-199a-3p/145-5p, which are relatively highly expressed promoted PC12 cell differentiation suppressed lipopolysaccharide (LPS) vitro through modulation NGF/TrkA pathway. also that Cblb was direct target miR-199a-3p Cbl miR-145-5p. gene knockdown resulted significantly decreased TrkA ubiquitination levels, subsequently activating downstream pathways Akt Erk. Conversely, overexpression associated with increased level, inactivating Western blot coimmunoprecipitation assays confirmed interaction between Cbl. In experiment, found upregulate expression at site promote locomotor function rats. Conclusions summary, our showed transferring into neurons rats affected signaling pathway, indicating hUC-MSC-derived may promising treatment strategy SCI.