title: Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury.
abstract: BACKGROUND
  The administration of stem cells holds promise as a potential therapy for spinal cord injury (SCI). Mesenchymal stem cells have advantages for clinical applications, since they can be easily obtained, are suitable for autologous transplantation and have been previously shown to induce regeneration of the spinal cord in experimental settings. Here we evaluated the feasibility, safety and potential efficacy of autologous transplantation of mesenchymal stem cells in subjects with chronic complete SCI.
  
  
  METHODS
  We conducted a phase I, non-controlled study in 14 subjects of both genders aging between 18 to 65 years, with chronic traumatic SCI (>6 months), at thoracic or lumbar levels, classified as American Spinal Injury Association (ASIA) A - complete injury. Baseline somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Pain rating was performed using the McGill Pain Questionnaire and a visual analogue score scale. Bone marrow-derived mesenchymal stem cells were cultured and characterized by flow cytometry, cell differentiation assays and G-band karyotyping. Mesenchymal stem cells were injected directly into the lesion following laminectomy and durotomy.
  
  
  RESULTS
  Cell transplantation was an overall safe and well-tolerated procedure. All subjects displayed variable improvements in tactile sensitivity and eight subjects developed lower limbs motor functional gains, principally in the hip flexors. Seven subjects presented sacral sparing and improved American Spinal Injury Association impairment scale (AIS) grades to B or C - incomplete injury. Nine subjects had improvements in urologic function. One subject presented changes in SSEP 3 and 6 months after mesenchymal stem cells transplantation. Statistically significant correlations between the improvements in neurological function and both injury size and level were found.
  
  
  CONCLUSIONS
  Intralesional transplantation of autologous mesenchymal stem cells in subjects with chronic, complete spinal cord injury is safe, feasible, and may promote neurological improvements.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01325103 - Registered 28 March 2011.
authors.forename: Marcus Vinícius Pinheiro
authors.initials: MV
authors.lastname: Mendonça
authors.forename: Ticiana Ferreira
authors.initials: TF
authors.lastname: Larocca
authors.forename: Bruno Solano
authors.initials: BS
authors.lastname: de Freitas Souza
authors.forename: Cristiane Flora
authors.initials: CF
authors.lastname: Villarreal
authors.forename: Luiz Flávio Maia
authors.initials: LF
authors.lastname: Silva
authors.forename: André Costa
authors.initials: AC
authors.lastname: Matos
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Novaes
authors.forename: Cláudia Maria Pinheiro
authors.initials: CM
authors.lastname: Bahia
authors.forename: Ana Carine
authors.initials: AC
authors.lastname: de Oliveira Melo Martinez
authors.forename: Carla Martins
authors.initials: CM
authors.lastname: Kaneto
authors.forename: Sissi Brandão Carneiro
authors.initials: SB
authors.lastname: Furtado
authors.forename: Geraldo Pedral
authors.initials: GP
authors.lastname: Sampaio
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
authors.forename: Ricardo Ribeiro
authors.initials: RR
authors.lastname: dos Santos
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D013119:Spinal Cord Injuries / Q000628:therapy*; D014182:Transplantation, Autologous / Q000009:adverse effects