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Mesenchymal stem cells from pediatric patients (pMSCs) are an attractive cell source in regenerative medicine, due to their higher proliferation rates and better differentiation abilities compared to adult MSCs (aMSCs). We have previously characterized the immunomodulatory abilities of pMSCs on T cells under co-culture. It has also been reported that aMSCs can inhibit B cell proliferation and maturation under inflammatory conditions. In this study, we therefore aimed to clarify the immunomodulatory effect of pMSCs toward T and B cells in an inflammatory microenvironment. Bone marrow derived pMSCs were primed to simulate inflammatory conditions by exposure with 50 ng/mL of IFN-? for 3 days. To analyze the interaction between pMSCs and T cells, CD3/CD28 stimulated peripheral blood mononuclear cells (PBMCs) were co-cultured with primed or unprimed pMSCs. To investigate B cell responses, quiescent B cells obtained from spleens by CD43 negative selection were stimulated with anti-IgM, anti-CD40, IL-2, and co-cultured with either IFN-? primed or unprimed pMSC. pMSC phenotype, B and T cell proliferation, and B cell functionality were analyzed. Gene expression of indoleamine 2,3-dioxygenease (IDO), as well as the expression of HLA-ABC, HLA-DR and the co-stimulatory molecules CD80 and CD86 was upregulated on pMSCs upon IFN-? priming. IFN-? did not alter the immunomodulatory abilities of pMSCs upon CD4(+) nor CD8(+) stimulated T cells compared to unprimed pMSCs. IFN-? primed pMSCs but not unprimed pMSCs strongly inhibited naïve (CD19(+)CD27(-)), memory (CD19(+)CD27(+)), and total B cell proliferation. Antibody-producing plasmablast (CD19(+)CD27(high)CD38(high)) formation and IgG production were also significantly inhibited by IFN-? primed pMSCs compared to unprimed pMSCs. Collectively, these results show that pMSCs have immunomodulatory effects upon the adaptive immune response which can be potentiated by inflammatory stimuli. This knowledge is useful in regenerative medicine and allogeneic transplantation applications toward tailoring pMSCs function to best modulate the immune response for a successful implant engraftment and avoidance of a strong immune reaction.

The goal of this internship is threefold. First there is an assignment to compare two vehicle dynamics simulation software packages, a Simulink two track model provided by the TU/e and a commercial multibody full vehicle model from dSPACE. For this comparison use is made of a chassis tuning project, which is also part of this internship. The TU/e two track model does not contain kinematics and elasto-kinematics, so the preference is given to the dSPACE multibody model. Another nice feature in this package is the possibility for animation of the simulation results. The second project is a hybrid sportscar project. Here the question is two determine which configuration, rear wheel driven or all wheel driven, is the best choice for converting a current sportscar model to a hybrid variant. The decision is based on a test were the vehicle enters a corner at 50 km/h and starts accelerating full throttle at the beginning of that corner. From the results at the exit of the corner can be concluded that the all wheel driven variant is the faster vehicle. Although the traction control system development was a difficult process and a lot of improvements are still possible, the final settings enable the all wheel driven variant to have an exit speed which is 6 km/h higher than the rear wheel driven variant. Here the recommendation is made to optimize the chassis setup for all wheel drive and preferably to use better front tyres. These measures will even further increase the difference and in the simulations the speed difference at the corner exit increases to 15 km/h. The third and final part of this internship was to simulate the influence of an additional battery pack on the dynamic behaviour of a hybrid vehicle. This hybrid vehicle has to be compared with the original vehicle. Measures are taken to decrease this influence and to make the dynamic behaviour of the hybrid vehicle similar to the that of the original vehicle. The influence of adding the additional battery pack is that the unmodified hybrid vehicle is oversteered more and also has some time delay in the lateral acceleration. The measures taken to reduce these effects are adding 0.5 degrees negative camber on the rear wheels, increasing the front roll stiffness with 20% and finally decreasing the rear roll stiffness with 30%. These measures appear to make the hybrid vehicle behave similar to the original vehicle, but real life tests should be performed to check if these measures suffice and if they are feasible with respect to other characteristics (eg. ride comfort).

Item does not contain fulltext R. Kraaijeveld Laagland. Globe: literatuur voor de tweede fase, Nederlands. VWO informatie- en verwerkingsboek. En: Laagland Literatuur Nederlands voor de tweede fase. HAVO informatie- en verwerkingsboek Zutphen:Thieme ,1999 90 03 23510 4