title: Neurogenin 2 converts mesenchymal stem cells into a neural precursor fate and improves functional recovery after experimental stroke.
abstract: BACKGROUND
  Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. Here, we investigated whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the therapeutic effects of MSCs after experimental stroke.
  
  
  METHODS
  In vitro, MSCs were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction, cells were identified by immunocytochemistry, Western blot and electrophysiological analyses. In a stroke model induced by transient right middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected 1 day after MCAO. Behavioral tests, neurological and immunohistochemical assessments were performed.
  
  
  RESULTS
  In vitro, Ngn2-MSCs expressed neural stem cells markers (Pax6 and nestin) and lost the potential to differentiate into mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs treated animals showed the highest functional recovery among the three groups.
  
  
  CONCLUSIONS
  Ngn2 was sufficient to convert MSCs into a neural precursor fate and transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Xiao Cheng
authors.initials: XC
authors.lastname: Lu
authors.forename: Huai Yong
authors.initials: HY
authors.lastname: Hao
authors.forename: Xue Liang
authors.initials: XL
authors.lastname: Dai
authors.forename: Teng Da
authors.initials: TD
authors.lastname: Qian
authors.forename: Bao Sheng
authors.initials: BS
authors.lastname: Huang
authors.forename: Lin Jun
authors.initials: LJ
authors.lastname: Tang
authors.forename: Wan
authors.initials: W
authors.lastname: Yu
authors.forename: Li Xin
authors.initials: LX
authors.lastname: Li
mesh_terms: D064591:Allografts; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C534807:Neurog2 protein, rat