For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
27
references
 Top references
cited by
38
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      99
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures.

          Patients and methods

          In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x10 6cells/kg) or high-dose(4x10 6cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded.

          Results

          Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy.

          Conclusion

          Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.

          Dimitrios Karussis, Clementine Karageorgiou, Adi Vaknin-Dembinsky … (2010)
          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). 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 × 10(6) (2.5 × 10(6)) MSCs was injected intrathecally (n = 34) and intravenously (n = 14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). 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. Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS 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). 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. Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects. Trial Registration  clinicaltrials.gov Identifier: NCT00781872.
          Article 0 comments Cited 283 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke.

            Jin Soo Lee, Ji Hong, Gyeong Joon Moon … (2010)
            We previously evaluated the short-term follow-up preliminary data of mesenchymal stem cells (MSCs) transplantation in patients with ischemic stroke. The present study was conducted to evaluate the long-term safety and efficacy of i.v. MSCs transplantation in a larger population. To accomplish this, we performed an open-label, observer-blinded clinical trial of 85 patients with severe middle cerebral artery territory infarct. Patients were randomly allocated to one of two groups, those who received i.v. autologous ex vivo cultured MSCs (MSC group) or those who did not (control group), and followed for up to 5 years. Mortality of any cause, long-term side effects, and new-onset comorbidities were monitored. Of the 52 patients who were finally included in this study, 16 were the MSC group and 36 were the control group. Four (25%) patients in the MSC group and 21 (58.3%) in the control group died during the follow-up period, and the cumulative surviving portion at 260 weeks was 0.72 in the MSC group and 0.34 in the control group (log-rank; p = .058). Significant side effects were not observed following MSC treatment. The occurrence of comorbidities including seizures and recurrent vascular episodes did not differ between groups. When compared with the control group, the follow-up modified Rankin Scale (mRS) score was decreased, whereas the number of patients with a mRS of 0-3 increased in the MSC group (p = .046). Clinical improvement in the MSC group was associated with serum levels of stromal cell-derived factor-1 and the degree of involvement of the subventricular region of the lateral ventricle. Intravenous autologous MSCs transplantation was safe for stroke patients during long-term follow-up. This therapy may improve recovery after stroke depending on the specific characteristics of the patients.
            Article 0 comments Cited 272 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis.

              Lianhua Bai, Donald P. Lennon, Valerie Eaton … (2009)
              Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC-induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together, these data suggest that the BM-hMSCs represent a viable option for therapeutic approaches.
              Article 0 comments Cited 165 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Oscar Fernández:
                ORCID: http://orcid.org/0000-0003-3696-789X
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Guillermo Izquierdo: Role: InvestigationRole: Writing – review & editing
                Victoria Fernández: Role: Data curationRole: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Laura Leyva: Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Virginia Reyes: Role: InvestigationRole: Writing – review & editing
                Miguel Guerrero: Role: InvestigationRole: Writing – review & editing
                Antonio León: Role: InvestigationRole: Writing – review & editing
                Carlos Arnaiz: Role: InvestigationRole: Writing – review & editing
                Guillermo Navarro: Role: InvestigationRole: Writing – review & editing
                Maria Dolores Páramo: Role: InvestigationRole: Writing – review & editing
                Antonio De la Cuesta: Role: InvestigationRole: Writing – review & editing
                Bernat Soria: Role: ConceptualizationRole: InvestigationRole: Writing – review & editing
                Abdelkrim Hmadcha: Role: InvestigationRole: Writing – review & editing
                David Pozo: Role: Investigation
                Rafael Fernandez-Montesinos: Role: InvestigationRole: Writing – review & editing
                Maria Leal: Role: InvestigationRole: Writing – review & editing
                Itziar Ochotorena: Role: InvestigationRole: Writing – review & editing
                Patricia Gálvez: Role: InvestigationRole: Writing – review & editing
                Maria Angeles Geniz: Role: InvestigationRole: Writing – review & editing
                Francisco Javier Barón: Role: Formal analysis
                Rosario Mata: Role: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Cristina Medina: Role: Formal analysisRole: Writing – review & editing
                Carlos Caparrós-Escudero: Role: InvestigationRole: Writing – review & editing
                Ana Cardesa: Role: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Natividad Cuende: Role: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Tim Friede: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 16 May 2018
                Publication date Collection: 2018
                Volume: 13
                Issue: 5
                Electronic Location Identifier: e0195891
                Affiliations
                [1 ] Unidad de Gestión Clínica de Neurociencias Clínicas, Servicio de Neurología y Servicio de Neurofisiología, Hospital Regional Universitario, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga, Malaga, Spain
                [2 ] Servicio de Neurología, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain
                [3 ] CABIMER (Andalusian Molecular Biology and Regenerative Medicine Centre), Seville, Spain
                [4 ] Public Health Department, University of Malaga, Malaga, SPAIN
                [5 ] Andalusian Initiative for Advanced Therapies, Junta de Andalucía, Seville, Spain
                [6 ] Servicio de Radiodiagnóstico, Hospital Universitario Virgen Macarena, University of Seville, Seville, Spain
                University Medical Center Gottingen, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ¶ Complete membership of the Research Group Study EudraCT 2008-004015-35 can be found in the Acknowledgments.

                Author information
                http://orcid.org/0000-0003-3696-789X
                Article
                Publisher ID: PONE-D-17-21058
                DOI: 10.1371/journal.pone.0195891
                PMC ID: 5955528
                PubMed ID: 29768414
                SO-VID: 96ddce31-54e3-4d8b-b097-48ec6884e01a
                Copyright © © 2018 Fernández et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 28 June 2017
                Date accepted : 26 March 2018
                Page count
                Figures: 1, Tables: 3, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: EC08/00224-ISCIII
                Award Recipient : O Fernández
                Funded by: Fondos Feder
                Award ID: FIS PI14/01015; RD/oo19/0028 and RD16/0011/0034
                Award Recipient :
                Funded by: Fondos Feder
                Award ID: PI16/00259
                Award Recipient : Abdelkrim Hamdcha
                This work was supported by Instituto de Salud Carlos III, Ministry of Health – Spain – Grant number: EC08/00224-ISCIII; Grants from ISCIII cofunded by Fondos FEDER, FIS PI14/01015; RD/oo19/0028 and RD16/0011/0034 to B Soria and PI16/00259 to A Hmadcha. The sponsor was the Andalusian Initiative for Advanced Therapies, supported by the Andalusian Health and Progress Foundation.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Research and Analysis Methods
                Subject: Imaging Techniques
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Medicine and Health Sciences
                Subject: Radiology and Imaging
                Subject: Diagnostic Radiology
                Subject: Magnetic Resonance Imaging
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Stem Cells
                Subject: Mesenchymal Stem Cells
                Subject: Medicine and Health Sciences
                Subject: Pulmonology
                Subject: Respiratory Infections
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Electrophysiology
                Subject: Membrane Potential
                Subject: Evoked Potentials
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Electrophysiology
                Subject: Membrane Potential
                Subject: Evoked Potentials
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Electrophysiology
                Subject: Neurophysiology
                Subject: Evoked Potentials
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Electrophysiology
                Subject: Neurophysiology
                Subject: Evoked Potentials
                Subject: Biology and Life Sciences
                Subject: Neuroscience
                Subject: Neurophysiology
                Subject: Evoked Potentials
                Subject: Medicine and Health Sciences
                Subject: Clinical Medicine
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Multiple Sclerosis
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Multiple Sclerosis
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Clinical Immunology
                Subject: Autoimmune Diseases
                Subject: Multiple Sclerosis
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Demyelinating Disorders
                Subject: Multiple Sclerosis
                Subject: Medicine and Health Sciences
                Subject: Neurology
                Subject: Neurodegenerative Diseases
                Subject: Multiple Sclerosis
                Subject: Medicine and Health Sciences
                Subject: Clinical Genetics
                Subject: Stem Cell Therapy
                Subject: Medicine and Health Sciences
                Subject: Diagnostic Medicine
                Subject: Signs and Symptoms
                Subject: Lesions
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Signs and Symptoms
                Subject: Lesions
                Subject: Medicine and Health Sciences
                Subject: Surgical and Invasive Medical Procedures
                Subject: Blood and Lymphatic System Procedures
                Subject: Stem Cell Transplantation
                Subject: Medicine and Health Sciences
                Subject: Surgical and Invasive Medical Procedures
                Subject: Transplantation
                Subject: Cell Transplantation
                Subject: Stem Cell Transplantation
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content99

                See all similar

                Cited by53

                See all cited by

                Most referenced authors897

                See all reference authors