title: Nucleus pulposus degeneration alters properties of resident progenitor cells.
abstract: BACKGROUND
  The intervertebral disc (IVD) possesses a minimal capability for self-repair and regeneration. Changes in the differentiation of resident progenitor cells can represent diminished tissue regeneration and a loss of homeostasis. We previously showed that progenitor cells reside in the nucleus pulposus (NP). The effect of the degenerative process on these cells remains unclear.
  
  
  OBJECTIVE
  We sought to explore the effect of IVD degeneration on the abundance of resident progenitor cells in the NP, their differentiation potential, and their ability to give rise to NP-like cells. We hypothesize that disc degeneration affects those properties.
  
  
  METHODS
  Nucleus pulposus cells derived from healthy and degenerated discs were methodically compared for proliferation, differentiation potential, and ability to generate NP-like cells.
  
  
  METHODS
  Intervertebral disc degeneration was induced in 10 skeletally, mature mini pigs using annular injury approach. Degeneration was induced in three target discs, whereas intact adjacent discs served as controls. The disc degeneration was monitored using magnetic resonance imaging for 6 to 8 weeks. After there was a clear evidence of degeneration, we isolated and compared cells from degenerated discs (D-NP cells [NP-derived cells from porcine degenerated discs]) with cells isolated from healthy discs (H-NP cells) obtained from the same animal.
  
  
  RESULTS
  The comparison showed that D-NP cells had a significantly higher colony-forming unit rate and a higher proliferation rate in vitro. Our data also indicate that although both cell types are able to differentiate into mesenchymal lineages, H-NP cells exhibit significantly greater differentiation toward the chondrogenic lineage and NP-like cells than D-NP cells, displaying greater production of glycosaminoglycans and higher gene expression of aggrecan and collagen IIa.
  
  
  CONCLUSIONS
  Based on these findings, we conclude that IVD degeneration has a meaningful effect on the cells in the NP. D-NP cells clearly go through the regenerative process; however, this process is not powerful enough to facilitate full regeneration of the disc and reverse the degenerative course. These findings facilitate deeper understanding of the IVD degeneration process and trigger further studies that will contribute to development of novel therapies for IVD degeneration.
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University-Hadassah, Faculty of Dental Medicine, PO BOX 12272, Jerusalem 91120, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Mizrahi
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.forename: Shiran
authors.initials: S
authors.lastname: Ben-David
authors.forename: Susan
authors.initials: S
authors.lastname: Su
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Anthony
authors.initials: A
authors.lastname: Oh
authors.forename: Hyun
authors.initials: H
authors.lastname: Bae
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D053687:Adult Stem Cells / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D007403:Intervertebral Disc / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000473:pathology*; D010012:Osteogenesis / Q000502:physiology*; D013552:Swine
keywords: Differentiation; Intervertebral disc degeneration; Nucleus pulposus; Progenitor cells; Proliferation