title: A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting Phase I human trials.
abstract: BACKGROUND
  There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs-either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model.
  
  
  METHODS
  Autologous adipose-derived MSCs (or artificial CSF) were delivered intrathecally, either with single or with repeated injections into the foramen magnum of healthy rabbits and monitored for 4 and 12 weeks, respectively.
  
  
  RESULTS
  Rabbits tolerated injections well and no definitive MSC-related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count data were normal and there were no differences in CSF interleukin-6 levels in all groups tested.
  
  
  CONCLUSIONS
  Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study have supported two successful investigational new drug applications to the Food and Drug Administration, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Bingkun K
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Staff
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jarred J
authors.initials: JJ
authors.lastname: Nesbitt
authors.affiliation: Human Cell Therapy Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Greg W
authors.initials: GW
authors.lastname: Butler
authors.affiliation: Human Cell Therapy Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Padley
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Human Cell Therapy Laboratory, Mayo Clinic, Rochester, Minnesota.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000628:therapy; D000818:Animals; D002478:Cells, Cultured; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D019578:Multiple System Atrophy / Q000378:metabolism / Q000628:therapy; D009929:Organ Size; D011817:Rabbits
chemical_list: D015850:Interleukin-6