Jeffrey A Cohen1, Peter B Imrey2, Sarah M Planchon1, Robert A Bermel1, Elizabeth Fisher3, Robert J Fox1, Amit Bar-Or4, Susan L Sharp1, Thomai T Skaramagas1, Patricia Jagodnik5, Matt Karafa6, Shannon Morrison6, Jane Reese Koc7, Stanton L Gerson7, Hillard M Lazarus7. 1. Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. 2. 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. 3. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA/Biogen, Cambridge, MA, USA. 4. Montreal Neurological Institute, McGill University, Montreal, QC, Canada/Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA. 5. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 6. Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 7. 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.
Abstract
BACKGROUND: 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. OBJECTIVE: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. METHODS: 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 × 106 MSCs/kg were thawed and administered IV. RESULTS: 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 × 106 MSCs/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. CONCLUSION: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
BACKGROUND: 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. OBJECTIVE: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. METHODS: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 × 106 MSCs/kg were thawed and administered IV. RESULTS: 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 × 106 MSCs/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. CONCLUSION: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.
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