title: Functional recovery after spinal cord injury in dogs treated with a combination of Matrigel and neural-induced adipose-derived mesenchymal Stem cells.
abstract: OBJECTIVE
  Previous studies have reported that scaffold or cell-based transplantation may improve functional recovery following spinal cord injury (SCI), but these results were based on neuronal regeneration and cell replacement. In this study, we investigated whether a combination of Matrigel and neural-induced mesenchymal stem cells (NMSC) improved hindlimb function in dogs with SCI, and what mechanisms were involved.
  
  
  METHODS
  We pre-differentiated canine adipose-derived mesenchymal stem cells into NMSC. A total of 12 dogs subjected to SCI procedures were assigned to one of the following three transplantation treatment groups: phosphate-buffered saline (PBS); Matrigel; or Matrigel seeded with NMSC. Treatment occurred 1 week after SCI. Basso, Beattie and Bresnahan (B.B.B.) and Tarlov scores, histopathology, immunofluorescence staining and Western blot analysis were used to evaluate the treatment effects.
  
  
  RESULTS
  Compared with dogs administered PBS or Matrigel alone, dogs treated with Matrigel + NMSC showed significantly better functional recovery 8 weeks after transplantation. Histology and immunochemical analysis revealed that the combination of Matrigel + NMSC reduced fibrosis from secondary injury processes and improved neuronal regeneration more than the other treatments. In addition, the combination of Matrigel + NMSC decreased the expression of inflammation and/or astrogliosis markers. Increased expressions of intracellular molecules related to neuronal extension, neuronal markers and neurotrophic factors were also found in the Matrigel + NMSC group. However, the expression of nestin as a neural stem cell marker was increased with Matrigel alone.
  
  
  CONCLUSIONS
  The combination of Matrigel + NMSC produced beneficial effects in dogs with regard to functional recovery following SCI through enhancement of anti-inflammation, anti-astrogliosis, neuronal extension and neuronal regeneration effects.
authors.affiliation: Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Park
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Donghae
authors.initials: D
authors.lastname: Lee
authors.forename: Kyuseok
authors.initials: K
authors.lastname: Choi
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Kim
authors.forename: Oh-Kyeong
authors.initials: OK
authors.lastname: Kweon
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D003094:Collagen / Q000627:therapeutic use; D004285:Dogs; D004338:Drug Combinations; D015870:Gene Expression; D006614:Hindlimb / Q000503:physiopathology; D007797:Laminin / Q000627:therapeutic use; D045164:Mesenchymal Stem Cell Transplantation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011509:Proteoglycans / Q000627:therapeutic use; D044968:Regenerative Medicine; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen