title: Effects of radial compression on a novel simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus fibrosus regeneration.
abstract: METHODS
  The aim of this study was to develop a tissue engineering approach in regenerating the annulus fibrosus (AF) as part of an overall strategy to produce a tissue-engineered intervertebral disc (IVD) replacement.
  
  
  OBJECTIVE
  To determine whether a rehabilitative simulation regime on bone marrow–derived mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF.
  
  
  BACKGROUND
  No previous study has used bone marrow–derived mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to regenerate the AF.
  
  
  METHODS
  The approach was to use bone marrow–derived stem cells to form cell-sheets and incorporating them onto silk scaffolds to simulate the native lamellae of the AF. The in vitro experimental model used to study the efficacy of such a system was made up of the tissue engineering AF construct wrapped around a silicone disc to form a simulated IVD-like assembly. The assembly was cultured within a custom-designed bioreactor that provided a compressive mechanical stimulation onto the silicone disc. The silicone nucleus pulposus would bulge radially and compress the simulated AF to mimic the physiological conditions. The simulated IVD-like assembly was compressed using a rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each day.
  
  
  RESULTS
  With the rehabilitative regime, the cell-sheets remained viable but showed a decrease in cell numbers and viability. Gene expression analysis showed significant upregulation of IVD-related genes and there was an increased ratio of collagen type II to collagen type I found within the extracellular matrix.
  
  
  CONCLUSIONS
  The results suggested that a rehabilitative regime caused extensive remodeling to take place within the simulated IVD-like assembly, producing extracellular matrix similar to that found in the inner AF.
authors: Division of Bioengineering, National University of Singapore, Singapore. biesyse@nus.edu.sg
authors: Eugene Yong-Shun
authors: EY
authors: See
authors: Siew Lok
authors: SL
authors: Toh
authors: James Cho-Hong
authors: JC
authors: Goh
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000502:physiology*; D018929:Cell Culture Techniques; D002470:Cell Survival; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012828:Silicones / Q000737:chemistry; D047011:Silk / Q000737:chemistry; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D012828:Silicones; D047011:Silk