title: Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat.
abstract: BACKGROUND
  A growing number of studies have highlighted the potential of stem cell and more-differentiated neural cell transplantation as intriguing therapeutic approaches for neural repair after spinal cord injury (SCI).
  
  
  METHODS
  A conditionally immortalized neural stem cell line derived from human fetal spinal cord tissue (SPC-01) was used to treat a balloon-induced SCI. SPC-01 cells were implanted into the lesion 1 week after SCI. To determine the feasibility of tracking transplanted stem cells, a portion of the SPC-01 cells was labeled with poly-L-lysine-coated superparamagnetic iron-oxide nanoparticles, and the animals grafted with labeled cells underwent magnetic resonance imaging. Functional recovery was evaluated by using the BBB and plantar tests, and lesion morphology, endogenous axonal sprouting and graft survival, and differentiation were analyzed. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted SPC-01 cells on endogenous regenerative processes.
  
  
  RESULTS
  Transplanted animals displayed significant motor and sensory improvement 2 months after SCI, when the cells robustly survived in the lesion and partially filled the lesion cavity. qPCR revealed the increased expression of rat and human neurotrophin and motor neuron genes. The grafted cells were immunohistologically positive for glial fibrillary acidic protein (GFAP); however, we found 25% of the cells to be positive for Nkx6.1, an early motor neuron marker. Spared white matter and the robust sprouting of growth-associated protein 43 (GAP43)(+) axons were found in the host tissue. Four months after SCI, the grafted cells matured into Islet2(+) and choline acetyltransferase (ChAT)(+) neurons, and the graft was grown through with endogenous neurons. Grafted cells labeled with poly-L-lysine-coated superparamagnetic nanoparticles before transplantation were detected in the lesion on T2-weighted images as hypointense spots that correlated with histologic staining for iron and the human mitochondrial marker MTCO2.
  
  
  CONCLUSIONS
  The transplantation of SPC-01 cells produced significant early functional improvement after SCI, suggesting an early neurotrophic action associated with long-term restoration of the host tissue, making the cells a promising candidate for future cell therapy in patients with SCI.
authors.forename: Takashi
authors.initials: T
authors.lastname: Amemori
authors.forename: Nataliya
authors.initials: N
authors.lastname: Romanyuk
authors.forename: Pavla
authors.initials: P
authors.lastname: Jendelova
authors.forename: Vit
authors.initials: V
authors.lastname: Herynek
authors.forename: Karolina
authors.initials: K
authors.lastname: Turnovcova
authors.forename: Pavel
authors.initials: P
authors.lastname: Prochazka
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kapcalova
authors.forename: Graham
authors.initials: G
authors.lastname: Cocks
authors.forename: Jack
authors.initials: J
authors.lastname: Price
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D009043:Motor Activity; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D014183:Transplantation, Heterologous
chemical_list: D058185:Magnetite Nanoparticles