Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION: Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI. METHODS: OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo. RESULTS: Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery. CONCLUSIONS: Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.

Suppression of TGFßR-Smad3 pathway alleviates the syrinx induced by syringomyelia.

BACKGROUND: Syringomyelia is a cerebrospinal fluid (CSF) disorder resulted in separation of pain and temperature, dilation of central canal and formation of syrinx in central canal. It is unclear about mechanisms of the dilation and syrinx formation. We aimed to investigate roles of ependymal cells lining central canal on the dilation, trying to reduce syrinx formation in central canal. METHODS: We employed 78 Sprague-Dawley (SD) rats totally with syringomyelia to detect the contribution of ependymal cells to the dilation of central canal. Immunofluorescence was used to examine the activation of ependymal cells in 54 syringomyelia rat models. BrdU was used to indicate the proliferation of ependymal cells through intraperitoneal administration in 6 syringomyelia rat models. 18 rats with syringomyelia were injected with SIS3, an inhibitor of TGFßR-Smad3, and rats injected with DMSO  were used as control. Among the 18 rats, 12 rats were used for observation of syrinx following SIS3 or DMSO administration by using magnetic resonance imaging (MRI) on day 14 and day 30 under syringomyelia without decompression. All the data were expressed as mean ± standard deviation (mean ± SD). Differences between groups were compared using the two-tailed Student's t-test or ANOVA. Differences were considered significant when *p < 0.05. RESULTS: Our study showed the dilation and protrusions of central canal on day 5 and enlargement from day 14 after syringomyelia induction in rats with activation of ependymal cells lining central canal. Moreover, the ependymal cells contributed to protrusion formation possibly through migration along with central canal. Furthermore, suppression of TGFßR-Smad3 which was crucial for migration reversed the size of syrnix in central canal without treatment of decompression, suggesting TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx. CONCLUSIONS: The size of syrinx was decreased after SIS3 administration without decompression. Our study depicted the mechanisms of syrinx formation and suggested TGFßR-Smad3 signal might be key for dilation of central canal and formation of syrinx.