title: Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: an open-label phase I trial.
abstract: OBJECTIVE
  Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion.
  
  
  METHODS
  In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow-derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733).
  
  
  RESULTS
  A median of 13.12 × 10(8) TNCs (range, 4.83-53.87) including 10.02 × 10(6) CD34+ cells (range, 1.02-29.9) in a volume of 7 mL (range, 4-10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10(8) TNCs (range, 1.36-17.85), with 3.39 × 10(6) cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found.
  
  
  CONCLUSIONS
  Subarachnoid placement of autologous bone marrow-derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México. Electronic address: consuelomanciasg@gmail.com.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Mancías-Guerra
authors.affiliation: Neuropediatrics Department, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Alma Rosa
authors.initials: AR
authors.lastname: Marroquín-Escamilla
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: González-Llano
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Laura
authors.initials: L
authors.lastname: Villarreal-Martínez
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Jaime-Pérez
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: García-Rodríguez
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Sagrario Lisete
authors.initials: SL
authors.lastname: Valdés-Burnes
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Laura Nely
authors.initials: LN
authors.lastname: Rodríguez-Romo
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Dinorah Catalina
authors.initials: DC
authors.lastname: Barrera-Morales
authors.affiliation: Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sánchez-Hernández
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Olga Graciela
authors.initials: OG
authors.lastname: Cantú-Rodríguez
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: César Homero
authors.initials: CH
authors.lastname: Gutiérrez-Aguirre
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Andrés
authors.initials: A
authors.lastname: Gómez-De León
authors.affiliation: Radiology and Imaging Department, Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Elizondo-Riojas
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: Rosario
authors.initials: R
authors.lastname: Salazar-Riojas
authors.affiliation: Hematology Service, Internal Medicine Department, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Monterrey, México.
authors.forename: David
authors.initials: D
authors.lastname: Gómez-Almaguer
mesh_terms: D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy; D002547:Cerebral Palsy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D014182:Transplantation, Autologous
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: autologous; brain injury; cellular therapy; cerebral palsy; intrathecal; stem cells