title: Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats.
abstract: BACKGROUND
  Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration.
  
  
  METHODS
  In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR.
  
  
  RESULTS
  Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction.
  
  
  CONCLUSIONS
  Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. amemori@biomed.cas.cz.
authors.forename: Takashi
authors.initials: T
authors.lastname: Amemori
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. j.ruzicka@biomed.cas.cz.|Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Plzenska 130/221, 150 00, Prague 5, Czech Republic. j.ruzicka@biomed.cas.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Ruzicka
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. romanyuk@biomed.cas.cz.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Romanyuk
authors.affiliation: Department of Neurosurgery, New York Medical College, Valhalla, NY, 10595, USA. meena.jhanwar1@gmail.com.
authors.forename: Meena
authors.initials: M
authors.lastname: Jhanwar-Uniyal
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. sykova@biomed.cas.cz.|Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Plzenska 130/221, 150 00, Prague 5, Czech Republic. sykova@biomed.cas.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic. jendel@biomed.cas.cz.|Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Plzenska 130/221, 150 00, Prague 5, Czech Republic. jendel@biomed.cas.cz.
authors.forename: Pavla
authors.initials: P
authors.lastname: Jendelova
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D007278:Injections, Spinal / Q000379:methods; D008124:Locomotion; D008297:Male; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D019899:Paracrine Communication; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D009419:Nerve Tissue Proteins