title: Bone marrow-derived mesenchymal stem cell transplantation for chronic spinal cord injury in rats: comparative study between intralesional and intravenous transplantation.
abstract: METHODS
  Animal experimental study.
  
  
  OBJECTIVE
  To present experimental evidence for mesenchymal cell therapy for spinal cord injury (SCI).
  
  
  BACKGROUND
  Prior to clinical application of stem cell therapy for SCI, many critical issues have to be addressed including efficiency, safety, method of transplantation, and differentiation of the transplanted cells.
  
  
  METHODS
  Chronic contusive SCI was induced in 36 Sprague-Dawley rats and randomly assigned to the intralesional (IL), intravenous (IV), or control groups. At 6 weeks post injury, allogenic mesenchymal stem cells (MSCs, 1 × 10 cells) were transplanted either intralesionally or intravenously for the intervention groups. Engraftment of the transplanted MSCs was evaluated with PKH 26 staining. Differentiation was evaluated using double stain with neuronal and glial cell markers. Brain-derived neurotrophic factor and nerve growth factor (NGF) were used for neurotrophic factor expression. Basso, Beattie, and Bresnahan locomotor rating scale was used for evaluation of functional recovery.
  
  
  RESULTS
  The estimated engraftment percentage of the transplanted cells in the IL group and IV group were 36.5%, and 15.5%, respectively. The engraftment of the transplanted MSCs was higher in the IL group than in the IV group. Most of the transplanted MSCs were colocalized with GFAP in both transplantation groups. Brain-derived neurotrophic factor and NGF expression (Western blot and real-time polymerase chain reaction) in the injured spinal cord was higher in both transplanted groups compared with those in the control group. At 6 weeks post transplantation, the mean Basso, Beattie, and Bresnahan locomotor scales in the IL, IV, and control groups were 5.63 ± 0.89, 5.63 ± 1.03, and 2.88 ± 0.44, respectively. The functional recovery seen in the rats that underwent transplantation was significantly better than that in the control group (P < 0.05).
  
  
  CONCLUSIONS
  Although the number of engrafted cells and expression of neurotrophic factors were lower in the IV group than those in the IL group, both IL and IV transplantation of MSC in the chronic SCI gave a significant clinical improvement. However, there were no differences in differentiation of the transplanted cells between the IL group and IV group. Astrocytic differentiation of the transplanted cells was predominant.
  
  
  METHODS
  N/A.
authors: Department of Orthopedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. boscoa@empal.com
authors: Jang-Woon
authors: JW
authors: Kim
authors: Kee-Yong
authors: KY
authors: Ha
authors: Jan Noel
authors: JN
authors: Molon
authors: Young-Hoon
authors: YH
authors: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D015870:Gene Expression; D006614:Hindlimb / Q000503:physiopathology; D006801:Humans; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020932:Nerve Growth Factor