@article{KleistMohrGaikwadetal.2016,
  author    = {Kleist, Christian and Mohr, Elisabeth and Gaikwad, Sadanand and Dittmar, Laura and Kuerten, Stefanie and Platten, Michael and Mier, Walter and Schmitt, Michael and Opelz, Gerhard and Terness, Peter},
  title     = {Autoantigen-specific immunosuppression with tolerogenic peripheral blood cells prevents relapses in a mouse model of relapsing-remitting multiple sclerosis},
  series = {Journal of Translational Medicine},
  volume    = {14},
  journal   = {Journal of Translational Medicine},
  number    = {99},
  doi       = {10.1186/s12967-016-0860-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165787},
  pages     = {1-14},
  year      = {2016},
  abstract  = {Background: Dendritic cells (DCs) rendered suppressive by treatment with mitomycin C and loaded with the autoantigen myelin basic protein demonstrated earlier their ability to prevent experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis (MS). This provides an approach for prophylactic vaccination against autoimmune diseases. For clinical application such DCs are difficult to generate and autoantigens hold the risk of exacerbating the disease. Methods: We replaced DCs by peripheral mononuclear cells and myelin autoantigens by glatiramer acetate (Copaxone ®), a drug approved for the treatment of MS. Spleen cells were loaded with Copaxone®, incubated with mitomycin C (MICCop) and injected into mice after the first bout of relapsing-remitting EAE. Immunosuppression mediated by MICCop was investigated in vivo by daily assessment of clinical signs of paralysis and in in vitro restimulation assays of peripheral immune cells. Cytokine profiling was performed by enzyme-linked immunosorbent assay (ELISA). Migration of MICCop cells after injection was examined by biodistribution analysis of 111Indium-labelled MICCop. The number and inhibitory activity of CD4+CD25+FoxP3+ regulatory T cells were analysed by histology, flow cytometry and in vitro mixed lymphocyte cultures. In order to assess the specificity of MICCop-induced suppression, treated EAE mice were challenged with the control protein ovalbumin. Humoral and cellular immune responses were then determined by ELISA and in vitro antigen restimulation assay. Results: MICCop cells were able to inhibit the harmful autoreactive T-cell response and prevented mice from further relapses without affecting general immune responses. Administered MICCop migrated to various organs leading to an increased infiltration of the spleen and the central nervous system with CD4+CD25+FoxP3+ cells displaying a suppressive cytokine profile and inhibiting T-cell responses. Conclusion: We describe a clinically applicable cell therapeutic approach for controlling relapses in autoimmune encephalomyelitis by specifically silencing the deleterious autoimmune response.},
  language  = {en}
}
@article{CanesiGiordanoLazzarietal.2016,
  author    = {Canesi, Margherita and Giordano, Rosaria and Lazzari, Lorenza and Isalberti, Maurizio and Isaias, Ioannis Ugo and Benti, Riccardo and Rampini, Paolo and Marotta, Giorgio and Colombo, Aurora and Cereda, Emanuele and Dipaola, Mariangela and Montemurro, Tiziana and Vigano, Mariele and Budelli, Silvia and Montelatici, Elisa and Lavazza, Cristiana and Cortelezzi, Agostino and Pezzoli, Gianni},
  title     = {Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy},
  series = {Journal of Translational Medicine},
  volume    = {14},
  journal   = {Journal of Translational Medicine},
  number    = {127},
  doi       = {10.1186/s12967-016-0880-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165725},
  pages     = {1-11},
  year      = {2016},
  abstract  = {Background: The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders. Methods: We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration. Results: One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up. Conclusions: We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach.},
  language  = {en}
}