MicroRNA‐126 (miR‐126), an endothelial‐specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR‐126‐based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR‐126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR‐126 (Exo‐miR‐126) by ultracentrifugation. In vitro study, Exo‐miR‐126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis‐related vascular endothelial growth factor (VEGF) and angiotensin‐1 (Ang‐1) were up‐regulated after incubation with Exo‐miR‐126. Additionally, the expression level of phosphoinositol‐3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR‐126 in HUVECs. Particularly, the Exo‐miR‐126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo‐miR‐126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR‐126 may be a promising strategy to promote angiogenesis.

Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.

Nasal olfactory mucosa mesenchymal stem cells (OM‐MSCs) have the ability to promote regeneration in the nervous system in vivo. Moreover, with view to the potential for clinical application, OM‐MSCs have the advantage of being easily accessible from patients and transplantable in an autologous manner, thus eliminating immune rejection and contentious ethical issues. So far, most studies have been focused on the role of OM‐MSCs in central nervous system replacement. However, the secreted proteomics of OM‐MSCs have not been reported yet. Here, proteins secreted by OM‐MSCs cultured in serum‐free conditions were separated on SDS‐PAGE and identified by LC‐MS/MS. As a result, a total of 274 secreted proteins were identified. These molecules are known to be important in neurotrophy, angiogenesis, cell growth, differentiation, and apoptosis, and inflammation which were highly correlated with the repair of central nervous system. The proteomic profiling of the OM‐MSCs secretome might provide new insights into their nature in the neural recovery. However, proteomic analysis for clinical biomarkers of OM‐MSCs needs to be further studied.

Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned medium (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors. Utilizing primary cell culture and murine models of SCI, we determined that systemic treatment with NSC-M was able to significantly improve motor function and lesion healing. In addition, NSC-M demonstrated significant anti-inflammatory potential in vitro and in vivo, reducing inflammatory cytokine expression in both activated macrophages and injured spinal cord tissues. NSC-M was also able to reduce the expression of inducible nitric oxide synthase (iNOS) within the spleen of injured animals, indicating an ability to reduce systemic inflammation. Thus, we believe that NSC-M offers a possible alternative to direct stem cell engraftment for the treatment of SCI.

Anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) are 2 effective and safe surgical treatments of degenerative cervical pathologies and are associated with a high percentage of excellent clinic...