title: Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis.
abstract: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest.
  
  
  
  To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS.
  
  
  
  Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 106MSCs/kg were thawed and administered IV.
  
  
  
  In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 106MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation.
  
  
  
  Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA/Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Imrey
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Planchon
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bermel
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA/Biogen, Cambridge, MA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Sharp
authors.affiliation: Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Thomai T
authors.initials: TT
authors.lastname: Skaramagas
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Jagodnik
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Karafa
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Case Comprehensive Cancer Center and National Center for Regenerative Medicine, Case Western Reserve University and Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Reese Koc
authors.affiliation: Case Comprehensive Cancer Center and National Center for Regenerative Medicine, Case Western Reserve University and Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
authors.forename: Stanton L
authors.initials: SL
authors.lastname: Gerson
authors.affiliation: Case Comprehensive Cancer Center and National Center for Regenerative Medicine, Case Western Reserve University and Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
mesh_terms: D000293:Adolescent; D000328:Adult; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D014182:Transplantation, Autologous / Q000379:methods; D055815:Young Adult
keywords: Multiple sclerosis; clinical trial; disability measures; mesenchymal stem cells; quantitative MRI; safety