A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. METHODS: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. RESULTS: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. CONCLUSIONS: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

Assessment of the combined effect of plasma exchange and plasma perfusion on patients with severe hepatitis awaiting orthotopic liver transplantation.

To determine if plasma exchange combined with plasma perfusion is a reliable and effective temporary liver support treatment for patients on the waiting list for OLT, we tested this method in 5 patients with end-stage and 3 patients with middle-stage severe hepatitis. Four patients were successfully controlled until a donor liver was available 4 to 13 days later. In contrast, the remaining 4 patients were not adequately controlled by this treatment and experienced aggravated disease progression, dying 3 to 8 days after treatment while still awaiting OLT. Of those 4 patients who received OLT, 2 patients died from multi-organ failure caused by hepatic failure, while the other 2 survived. These findings show that plasma exchange combined with plasma perfusion provides temporary support for some patients on the waiting list for OLT. The ability of patients to successfully bridge to OLT is closely associated with the degree of liver failure, complications, multi-organ failure, and the length of the waiting period for a donor liver.