Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

OBJECTIVE: Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Effica...

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Autores: Llufriu Duran, Sara, Sepúlveda, María, Blanco, Yolanda, Marín, Pedro, Moreno, Beatriz, Berenguer, Joan, Gabilondo, Iñigo, Martinez-Heras, Eloy, Sola Valls, Nuria, Arnaiz Gargallo, Juan Alberto, Andreu, Enrique J., Fernández, Begoña, Bullich Roig, Santiago, Sánchez Dalmau, Bernardo, Graus Ribas, Francesc, Villoslada, Pablo, Saiz Hinarejos, Albert
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/119441
Acesso em linha:https://hdl.handle.net/2445/119441
Access Level:acceso abierto
Palavra-chave:Cèl·lules mare
Esclerosi múltiple
Ressonància magnètica
Cèl·lules T
Cèl·lules B
Assaigs clínics
Stem cells
Multiple sclerosis
Magnetic resonance
T cells
B cells
Clinical trials
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repository_id_str
spelling Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.Llufriu Duran, SaraSepúlveda, MaríaBlanco, YolandaMarín, PedroMoreno, BeatrizBerenguer, JoanGabilondo, IñigoMartinez-Heras, EloySola Valls, NuriaArnaiz Gargallo, Juan AlbertoAndreu, Enrique J.Fernández, BegoñaBullich Roig, SantiagoSánchez Dalmau, BernardoGraus Ribas, FrancescVilloslada, PabloSaiz Hinarejos, AlbertCèl·lules mareEsclerosi múltipleRessonància magnèticaCèl·lules TCèl·lules BAssaigs clínicsStem cellsMultiple sclerosisMagnetic resonanceT cellsB cellsClinical trialsOBJECTIVE: Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. METHODS: Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. RESULTS: At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. CONCLUSION: Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.Public Library of Science (PLoS)2018201820142018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/119441Articles publicats en revistes (Fonaments Clínics)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0113936PLoS One, 2014, vol. 9, num. 12, p. e113936https://doi.org/10.1371/journal.pone.0113936cc-by (c) Llufriu Duran, Sara et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1194412026-05-29T05:05:01Z
dc.title.none.fl_str_mv Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
title Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
spellingShingle Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
Llufriu Duran, Sara
Cèl·lules mare
Esclerosi múltiple
Ressonància magnètica
Cèl·lules T
Cèl·lules B
Assaigs clínics
Stem cells
Multiple sclerosis
Magnetic resonance
T cells
B cells
Clinical trials
title_short Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
title_full Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
title_fullStr Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
title_full_unstemmed Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
title_sort Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.
dc.creator.none.fl_str_mv Llufriu Duran, Sara
Sepúlveda, María
Blanco, Yolanda
Marín, Pedro
Moreno, Beatriz
Berenguer, Joan
Gabilondo, Iñigo
Martinez-Heras, Eloy
Sola Valls, Nuria
Arnaiz Gargallo, Juan Alberto
Andreu, Enrique J.
Fernández, Begoña
Bullich Roig, Santiago
Sánchez Dalmau, Bernardo
Graus Ribas, Francesc
Villoslada, Pablo
Saiz Hinarejos, Albert
author Llufriu Duran, Sara
author_facet Llufriu Duran, Sara
Sepúlveda, María
Blanco, Yolanda
Marín, Pedro
Moreno, Beatriz
Berenguer, Joan
Gabilondo, Iñigo
Martinez-Heras, Eloy
Sola Valls, Nuria
Arnaiz Gargallo, Juan Alberto
Andreu, Enrique J.
Fernández, Begoña
Bullich Roig, Santiago
Sánchez Dalmau, Bernardo
Graus Ribas, Francesc
Villoslada, Pablo
Saiz Hinarejos, Albert
author_role author
author2 Sepúlveda, María
Blanco, Yolanda
Marín, Pedro
Moreno, Beatriz
Berenguer, Joan
Gabilondo, Iñigo
Martinez-Heras, Eloy
Sola Valls, Nuria
Arnaiz Gargallo, Juan Alberto
Andreu, Enrique J.
Fernández, Begoña
Bullich Roig, Santiago
Sánchez Dalmau, Bernardo
Graus Ribas, Francesc
Villoslada, Pablo
Saiz Hinarejos, Albert
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules mare
Esclerosi múltiple
Ressonància magnètica
Cèl·lules T
Cèl·lules B
Assaigs clínics
Stem cells
Multiple sclerosis
Magnetic resonance
T cells
B cells
Clinical trials
topic Cèl·lules mare
Esclerosi múltiple
Ressonància magnètica
Cèl·lules T
Cèl·lules B
Assaigs clínics
Stem cells
Multiple sclerosis
Magnetic resonance
T cells
B cells
Clinical trials
description OBJECTIVE: Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. METHODS: Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. RESULTS: At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. CONCLUSION: Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.
publishDate 2014
dc.date.none.fl_str_mv 2014
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/119441
url https://hdl.handle.net/2445/119441
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0113936
PLoS One, 2014, vol. 9, num. 12, p. e113936
https://doi.org/10.1371/journal.pone.0113936
dc.rights.none.fl_str_mv cc-by (c) Llufriu Duran, Sara et al., 2014
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Llufriu Duran, Sara et al., 2014
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,228081

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