title: Transplanting p75-suppressed bone marrow stromal cells promotes functional behavior in a rat model of spinal cord injury.
abstract: Bone marrow stromal cells (BMSC) have been successfully employed for movement deficit recovery in spinal cord injury (SCI) rat models. One of the unsettled problems in cell transplantation is the relative high proportion of cell death, specifically after neural differentiation. According to our previous studies, p75 receptor, known as the death receptor, is only expressed in BMSC in a time window of 6-12 hours following neural induction. Moreover, we have recently reported a decreased level of apoptosis in p75-suppressed BMSC in vitro. Therefore, our objective in this research was to explore the functional effects of transplanting p75:siRNA expressing BMSC in SCI rats.
  
  
  
  Laminectomy was performed at L1 vertebra level to expose spinal cord for contusion using weight-drop method. PBS-treated SCI rats (group one) were used as negative controls, in which cavitations were observed 10 weeks after SCI. pRNA-U6.1/Hygro- (group two, as a mock) and pRNA-U6.1/Hygro-p75 shRNA- (group three) transfected BMSC were labeled with a fluorescent dye, CM-DiI, and grafted into the lesion site 7 days after surgery. The Basso-Beattie-Bresnehan locomotor rating scale was performed weekly for 10 weeks.
  
  
  
  There was a significant difference (P≤0.05) between all groups of treated rats regarding functional recovery. Specifically, the discrepancy among p75 siRNA and mock-transfected BMSC was statistically significant. P75 siRNA BMSC also revealed a higher level of in vivo survival compared to the mock BMSC.
  
  
  
  Our data suggest that genetically modified BMSC that express p75:siRNA could be a more suitable source of cells for treatment of SCI.
authors.affiliation: Dept. Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Houri
authors.initials: H
authors.lastname: Edalat
authors.affiliation: Dept. of Physiology, Aerospace Research Institute, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hajebrahimi
authors.affiliation: Dept. of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Pirhajati
authors.affiliation: Dept. of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Movahedin
authors.affiliation: Genetic Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Tavallaei
authors.affiliation: Janbazan Medical and Engineering Research Center, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Soroush
authors.affiliation: Dept. Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Seyed Javad
authors.initials: SJ
authors.lastname: Mowla
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002232:Carbocyanines / Q000378:metabolism; D019070:Cell Lineage; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D013194:Staining and Labeling; D014162:Transfection
chemical_list: C101089:CM-DiI; D002232:Carbocyanines; D020800:Receptor, Nerve Growth Factor
keywords: Spinal cord injury; Apoptosis; Bone marrow stromal cells