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Background The therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.Methods Using a mouse model of compression SCI, ADSCs and Jagged1 small interfering RNA (siRNA) were injected into the spinal cord. Locomotor function, spinal cord tissue morphology and the levels of various proteins and transcripts were compared between groups.Results ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium binding adapter molecule 1 (Iba1) and ED1 staining in the injured spinal cord, promoting the survival of neurons. These changes were accompanied by improved functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in a decrease in SCI-induced proinflammatory cytokines as well as the activation of microglia. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 following SCI.Conclusion The results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation.

Human umbilical cord mesenchymal stem cells (UCMSCs) have recently been shown to hold great therapeutic potential for the treatment of spinal cord injury (SCI). However, the number of engrafted cells has been shown to decrease dramatically post-transplantation. Physioxia is known to enhance the paracrine properties and immune modulation of stem cells, a notion that has been applied in many clinical settings. We therefore hypothesized that preconditioning of UCMSCs in physioxic environment would enhance the regenerative properties of these cells in the treatment of rat SCI. UCMSCs were pretreated with either atmospheric normoxia (21% O2, N-UCMSC) or physioxia (5% O2, P-UCMSC). The MSCs were characterized using flow cytometry, immunocytochemistry, and real-time polymerase chain reaction. Furthermore, 10(5) N-UCMSC or P-UCMSC were injected into the injured spinal cord immediately after SCI, and locomotor function as well as cellular, molecular and pathological changes were compared between the groups. We found that N-UCMSC and P-UCMSC displayed similar surface protein expression. P-UCMSC grew faster, while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs. Compared to N-UCMSC, treatment with P-UCMSC was associated with marked changes in the SCI environment, with a significant increase in axonal preservation and a decrease in the number of caspase-3+ cells and ED-1+ macrophages. These changes were accompanied by improved functional recovery. Thus, the present study indicated that preculturing UCMSCs under 5% lowered oxygen physioxic conditions prior to transplantation improves their therapeutic potential for the treatment of SCI in rats.