Reporter gene-expressing bone marrow-derived stromal cells are immune-tolerated following implantation in the central nervous system of syngeneic immunocompetent mice

<p>Abstract</p> <p>Background</p> <p>Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics.</p> <p>Results</p> <p>In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-γ-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation.</p> <p>Conclusion</p> <p>We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.</p

Identifying science students at risk in the first year of higher education: the incremental value of non-cognitive variables in predicting early academic achievement

Science students’ study success rates in the first year of higher education (FYHE) are problematic. Although a considerable amount of previous research has been carried out to investigate the determinants of students’ academic achievement in FYHE, there has been little discussion about the incremental value of non-cognitive factors over and above cognitive determinants in the prediction of early (after the first semester of FYHE) academic achievement in a science educational context. Furthermore, the complex nature of the relationships between determinants of academic achievement is frequently neglected. An investigation that addresses these gaps is important to provide the insights necessary to identify at-risk science students early in their academic career. Therefore, the main aim of this research was to examine the incremental value of non-cognitive variables (processing strategies, regulation strategies, academic motivation, self-concept, self-efficacy) in predicting students’ early academic achievement in a science FYHE context, over and above domain-specific prior knowledge (cognitive) and after controlling for gender, age and prior education. Hereto, path-analyses were used on the data of 781 first-year students within a faculty of science of a Belgian university college in the academic year 2016–2017. Results show that cognitive variables and pre-entry characteristics predict early academic achievement. However, after controlling for these characteristics, evidence for the assumption that non-cognitive variables are determinants of early academic achievement in science education contexts could not be found in this study. Implications for theory and research are discussed

Een vrije maar verantwoorde keuze : het nut van ijkingstoetsen

Bij de vrije toegang tot het Vlaamse hoger onderwijs spelen ijkingstoetsen een belangrijke rol. Ze geven aspirant-studenten handvatten om na te denken over hun studiekeuze. Ze leveren bovendien een bijdrage aan studie- en studentsucces, zo blijkt uit evaluaties

An evaluation of the effect of pulse-shape on grey and white matter stimulation in the rat brain

Despite the current success of neuromodulation, standard biphasic, rectangular pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared stimulation efficiency (in terms of charge) between complex and standard pulses in two areas of the rat brain. In motor cortex, Gaussian and interphase gap stimulation (IPG) increased stimulation efficiency in terms of charge per phase compared with a standard pulse. Moreover, IPG stimulation of the deep mesencephalic reticular formation in freely moving rats was more efficient compared to a standard pulse. We therefore conclude that complex pulses are superior to standard stimulation, as less charge is required to achieve the same behavioral effects in a motor paradigm. These results have important implications for the understanding of electrical stimulation of the nervous system and open new perspectives for the design of the next generation of safe and efficient neural implants.status: publishe