title: Intervertebral disc-derived stem cells: implications for regenerative medicine and neural repair.
abstract: METHODS
  An in vitro and in vivo evaluation of intervertebral disc (IVD)-derived stem/progenitor cells.
  
  
  OBJECTIVE
  To determine the chondrogenic, adipogenic, osteogenic, and neurogenic differentiation capacity of disc-derived stem/progenitor cells in vitro and neurogenic differentiation in vivo.
  
  
  BACKGROUND
  Tissue repair strategies require a source of appropriate cells that could be used to replace dead or damaged cells and tissues such as stem cells. Here we examined the potential use of IVD-derived stem cells in regenerative medicine approaches and neural repair.
  
  
  METHODS
  Nonchondrodystrophic canine IVD nucleus pulposus (NP) cells were used to generate stem/progenitor cells (NP progenitor cells [NPPCs]) and the NPPCs were differentiated in vitro into chondrogenic, adipogenic, and neurogenic lineages and in vivo into the neurogenic lineage. NPPCs were compared with bone marrow-derived mesenchymal (stromal) stem cells in terms of the expression of stemness genes. The expression of the neural crest marker protein 0 and the Brachyury gene were evaluated in NP cells and NPPCs.
  
  
  RESULTS
  NPPCs contain stem/progenitor cells and express "stemness" genes such as Sox2, Oct3/4, Nanog, CD133, Nestin, and neural cell adhesion molecule but differ from mesenchymal (stromal) stem cells in the higher expression of the Nanog gene by NPPCs. NPPCs do not express protein 0 or the Brachyury gene both of which are expressed by the totality of IVD NP cells. The percentage of NPPCs within the IVD is 1% of the total as derived by colony-forming assay. NPPCs are capable of differentiating along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo within the compact myelin-deficient shiverer mouse.
  
  
  CONCLUSIONS
  We propose that the IVD NP represents a regenerative niche suggesting that the IVD could represent a readily accessible source of precursor cells for neural repair and regeneration.
authors: Division of Orthopaedic Surgery, University of Toronto, Toronto, Canada. mark.erwin@utoronto.ca
authors: W Mark
authors: WM
authors: Erwin
authors: Diana
authors: D
authors: Islam
authors: Eftekhar
authors: E
authors: Eftekarpour
authors: Robert D
authors: RD
authors: Inman
authors: Muhammad Zia
authors: MZ
authors: Karim
authors: Michael G
authors: MG
authors: Fehlings
mesh_terms: D000071916:AC133 Antigen; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004285:Dogs; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D010455:Peptides / Q000235:genetics; D044968:Regenerative Medicine / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D050814:Octamer Transcription Factor-3; D010455:Peptides; C000606024:Prom1 protein, mouse; D055748:SOXB1 Transcription Factors; D020825:T-Box Domain Proteins