Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis
Dimitrios Karussis, MD, PhD; Clementine Karageorgiou, MD; Adi Vaknin-Dembinsky, MD, PhD; Basan Gowda-Kurkalli, PhD; John M. Gomori, MD; Ibrahim Kassis, MSc; Jeff W. M. Bulte, PhD; Panayiota Petrou, MD; Tamir Ben-Hur, MD, PhD; Oded Abramsky, MD, PhD; Shimon Slavin, MD
La moitié st basés à Jérusalem, l'autre moitié à Baltimore (US)
Arch Neurol. 2010;67(10):1187-1194. doi:10.1001/archneurol.2010.248
Objective To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).
Design A phase 1/2 open-safety clinical trial.
Patients Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled.
Intervention After culture, a mean (SD) of 63.2 x 106 (2.5 x 106) MSCs was injected intrathecally (n = 34) and intravenously (n = 14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex).
Main Outcome Measures The main outcome measure was the recording of side effects. Follow-up (25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation.
Results Twenty-one patients had injection-related adverse effects (sur un total de 48 !) consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up (ds l'article y'en a qui marchent moins bien q'au début, ms c'est pas grave ! 4 sur 34 soit 11%). The mean ALSFRS (ça c'est pr les SLA) score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6) (wah, quelle amélioration !). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4+CD25+ regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40+, CD83+, CD86+, and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation.
Conclusion Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively (j'adore) safe procedure and induces immediate immunomodulatory effects.
Funding/Support: This work was supported by the
ECTRIMS Fellowship grant 2009-2010. Part of this study
was funded by NMSS RG3630 and TEDCOMDStem Cell
Fund ESC 06-29-01
Taduction, une autre fois ms globalement : effets 2aires lourds, (entre autre difficultés à la marche !), seulement 34 patients injectés, pas de sujets sains en contrôle (cf les critiques vis à vis Zambo), EDSS pr les 15 MS passe de 6,7 à 5,9 sur 25 mois, tu parles d'une amélioration, et vue la taille de la barre d'erreur c'est de la daube !!! Faut chercher dur pr trouver ça. D'ailleurs c'est pr mesurer l'EDSS q'ils se st le plus fait ch... si ça se trouve !
J'ai l'article entier en pdf, si d'aucuns st intéressés ! ms adresse mail par mp.