RT Journal Article
T1 Gene therapy with mesenchymal stem cells expressing IFN-ß ameliorates neuroinflammation in experimental models of multiple sclerosis.
A1 Marin-Bañasco, C
A1 Benabdellah, K
A1 Melero-Jerez, C
A1 Oliver, B
A1 Pinto-Medel, M J
A1 Hurtado-Guerrero, I
A1 de-Castro, F
A1 Clemente, D
A1 Fernandez, O
A1 Martin, F
A1 Leyva, L
A1 Suardiaz, M
K1 Mesenchymal Stem Cells
K1 Mice, Inbred C57BL
K1 Multiple Sclerosis, Chronic Progressive
K1 Multiple Sclerosis, Relapsing-Remitting
K1 Severity of Illness Index
AB Recombinant IFN-ß is one of the first-line treatments in multiple sclerosis (MS), despite its lack of efficacy in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, by taking advantage of their pathotropism, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues. Here, we report the therapeutic effect of systemic delivery of adipose-derived MSCs (AdMSCs), transduced with the IFN-β gene, into mice with experimental autoimmune encephalomyelitis (EAE). Relapsing-remitting and chronic progressive EAE were induced in mice. Cells were injected i.v. Disease severity, inflammation and tissue damage were assessed clinically, by flow cytometry of spleens and histopathological evaluation of the CNS respectively. Genetic engineering did not modify the biological characteristics of these AdMSCs (morphology, growth rate, immunophenotype and multipotency). Furthermore, the transduction of IFN-ß to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuro-inflammation. Gene therapy was found to be more effective than cell therapy in ameliorating several clinical parameters in both EAE models, presumably due to the continuous expression of IFN-β. Furthermore, it has significant advantages over AdMSC therapy, and also over systemic IFN-ß treatment, by providing long-term expression of the cytokine at therapeutic concentrations and reducing the frequency of injections, while minimizing dose-limiting side effects.
PB John Wiley & Sons
YR 2017
FD 2017-01-18
LK http://hdl.handle.net/10668/10631
UL http://hdl.handle.net/10668/10631
LA en
NO Marin-Bañasco C, Benabdellah K, Melero-Jerez C, Oliver B, Pinto-Medel MJ, Hurtado-Guerrero I, et al. Gene therapy with mesenchymal stem cells expressing IFN-ß ameliorates neuroinflammation in experimental models of multiple sclerosis. Br J Pharmacol. 2017 Feb;174(3):238-253
NO This work was supportedby Fondo de Investigaciones Sanitarias ISCIII (Spain) andFondo Europeo de Desarrollo Regional (FEDER) from the Eu-ropean Union through the research grants PI12/01097 andPI15/00963 and ISCIII Red de Terapia Celular TerCelRD12/0019/0006 to F.M., by the Consejería de Economía,Innovación, Ciencia y Empleo, Junta de Andalucía-FEDER/Fondo de Cohesion Europeo (FSE) de Andalucía through theresearch grants P09-CTS-04532, PI-57069 and PAIDI-Bio-326to F.M. and PI-0160/2012 to K.B. M.J.P.-M. has been sup-ported by grants from Red Temática deInvestigaciónCooperativa Red Española de Esclerosis Múlti-ple REEM (RD07/0060 and RD12/0032). B.O. is financed bya contract from Excelent Project CTS-7670/11 fromConsejería de Economía, Innovación, Ciencia y Empleo(Junta de Andalucía).Author contributionsL.L., F.M. and M.S contributed to the design and concept ofthe study. C.M.-B., K.B., C.M.-J., B.O., I.H.-G., M.J.P.-M. andM.S performed the experiments. D.C., F.deC., O.F., L.L., F.M. and M.S analysed and interpreted the data. F.M, D.C.and M.S drafted the manuscript. L.L., O.F. and M.S revisedthe manuscript.BJP C Marin-Bañasco et al.250 British Journal of Pharmacology (2017) 174 238–253
DS RISalud
RD Apr 19, 2025