Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Olivia M. Torre, Victoria Mroz, Meredith K. Bartelstein, Alice H. Huang, James C. Iatridis

Research output: Contribution to journalReview articlepeer-review

66 Scopus citations


Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing.

Original languageEnglish
Pages (from-to)61-78
Number of pages18
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - Apr 2019


  • annulus fibrosus
  • cell phenotype
  • healing
  • intervertebral disk
  • intervertebral disk injury models
  • regeneration


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