Abstract
Objective: To investigate the influence of signal transducer and activator of transcription-3 (STAT3) on spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we wished to determine if STAT3 would be related to the pathogenesis of spina bifida aperta (SBA) and permit increased survival of spinal cord transplants to improve therapeutic efficiency of cellular transplantation from 20-day pregnant (E20) rats. Method: Spina bifida aperta were induced with a single intragastric retinoic acid (140 mg/kg body weight) administration on E10. STAT3 and caspase-8 expression, caspase-8 positive cells by immunofluorescence on 14, 15, 16 and 17 day in spinal cord of rat fetuses with control group and spina bifida aperta group are analysed. The pregnant rats received fetal surgery and microinjection of Mesenchymal Stem Cells (MSCs) after STAT3 transfection on 16-day pregnant (E16), 17-day pregnant (E17) and 18-day pregnant (E18), P0, P1-6 and to P7-12 of cell passages as well as different injected cell number, then sacrificed on 20-day pregnant (E20) for spine sample collection. The Number of each group was not less than seven. The spinal cord samples were collected directly to detect survival rates of MSCs and caspase-8 expression. Results: The developmental change in caspase-8 expression of spina bifida aperta was notably increased to the top on E15 compared with no SBA fetuses with Retinoic Acid. STAT3 expression in SBA rat fetuses gradually decreased with embryonic development between E14 and E15, E15 dropped down to bottom. Specifically, the number of caspase-8 positive cells on E15 in spinal cord with SBA rat fetuses was the most; and from E16, the positive cells began to decrease. Compared with STAT3 non-transfection group, MSCs combined with STAT3 transfection on E18, P7-12 and medium injection cell number can statistically improve the success rate of transplantation. In addition, caspase-8 mRNA and protein levels were significantly decreased in STAT3 transfection transplantation contrast for SBA of cellular culture medium and STAT3 non-transfection transplantation. Conclusions: STAT3 may be associated with the pathogenesis of spina bifida aperta. Furthermore, MSCs transplantation after STAT3 transfection can increase survival rates and reduce apoptosis in the spinal column through caspase-8.
STAT3 Regulates the Pathogenesis and Bone Mesenchymal Stem Cells Transplantation of Spina Bifida Aperta Through Caspase-8
