Decellularised nucleus pulposus as a potential biologic scaffold for disc tissue engineering

Mater Sci Eng C Mater Biol Appl. 2019 Jun:99:1213-1225. doi: 10.1016/j.msec.2019.02.045. Epub 2019 Feb 16.

Abstract

Intervertebral disc (IVD) degeneration is associated with lower back pain, with the dysfunction of nucleus pulposus (NP) cells instigating degeneration onset. Here, we developed an optimized decellularised NP scaffold that could induce mesenchymal stem cells (MSCs) into NP-like cells in vitro and rescue the degenerated IVD in vivo. We optimized a decellularisation protocol for porcine NP and evaluated the biological properties and microstructure of the NP scaffold. Through co-culture with MSCs, we analysed scaffold bioactivity and potential signalling pathways. We tested the therapeutic efficacy of the scaffold using an IVD degeneration model in vivo. The decellularisation protocol generally removed the cellular components of the NP and preserved the majority of the biological components and regular microstructure. MSCs seeded in the NP-ECM scaffold differentiated into NP-like cells in vitro; this change was attributed to activation of the TGF-β signalling pathway. The NP-ECM exhibited good cytocompatibility ex vivo and decelerated the degeneration of the IVD in vivo. These results indicate the successful establishment of a naturally-derived ECM material that could induce MSCs into NP cells and serve as a potential treatment for degenerated IVDs.

Keywords: Decellularization; Degeneration; Intervertebral disc; Mesenchymal stem cell; Scaffold.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • DNA / metabolism
  • Extracellular Matrix / metabolism
  • Female
  • Humans
  • Intervertebral Disc Degeneration / pathology
  • Intervertebral Disc Degeneration / therapy
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Nucleus Pulposus / physiology*
  • Nucleus Pulposus / ultrastructure
  • Porosity
  • Rabbits
  • Regeneration
  • Signal Transduction
  • Swine
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • DNA