title: Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis.
abstract: There is a critical unmet need to develop regenerative therapies for the demyelinating disease multiple sclerosis (MS). We previously characterized the immunoregulatory and trophic properties of neural progenitors derived from bone marrow mesenchymal stromal cells (MSC-NPs) and established that cells derived from MS and non-MS patients alike were therapeutically viable. In an experimental model of MS, intrathecal MSC-NP injection resulted in disease amelioration with decreased T-cell infiltration, and less severe lesion pathology associated with recruitment of resident progenitors to inflammatory sites. In this pilot feasibility study, we investigated safety and dosing of intrathecal MSC-NP therapy in six patients with MS.
  
  
  
  Patients with progressive MS and advanced disability who were refractory to all other conventional MS treatments were enrolled in the study. For each dose, MSC-NP cells were cultured from autologous MSCs and tested for quality control before intrathecal administration. Patients were evaluated for adverse events and neurological status to assess safety of the treatment.
  
  
  
  Six patients with progressive MS were treated with between 2 and 5 intrathecal injections of escalating doses of autologous MSC-NPs and were followed an average of 7.4 years after initial injection. There were no safety concerns noted, no serious adverse events, and the multiple dosing regimen was well tolerated. Four of the six patients showed a measurable clinical improvement following MSC-NP treatment.
  
  
  
  This pilot study supports preliminary first-in-human safety and tolerability of autologous MSC-NP treatment for MS.
authors.affiliation: Tisch Multiple Sclerosis Research Center of New York, New York, NY, USA.
authors.forename: Violaine K
authors.initials: VK
authors.lastname: Harris
authors.affiliation: Tisch Multiple Sclerosis Research Center of New York, New York, NY, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Vyshkina
authors.affiliation: Tisch Multiple Sclerosis Research Center of New York, New York, NY, USA. Electronic address: ssadiq@tischms.org.
authors.forename: Saud A
authors.initials: SA
authors.lastname: Sadiq
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007278:Injections, Spinal / Q000009:adverse effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000628:therapy*; D000069442:Natalizumab / Q000627:therapeutic use; D058953:Neural Stem Cells / Q000637:transplantation*; D010865:Pilot Projects; D000069283:Rituximab / Q000627:therapeutic use; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D014182:Transplantation, Autologous
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D000069283:Rituximab; D008727:Methotrexate
keywords: autologous transplantation; mesenchymal stromal cells; multiple sclerosis; spinal injections; stem cell transplantation