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

Abstract

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.

TRPV4 Inhibition and CRISPR-Cas9 Knockout Reduce Inflammation Induced by Hyperphysiological Stretching in Human Annulus Fibrosus Cells

“…Mechanical stressors such as impact, heavy lifting, muscle activations, and work/lifestyle factors (e.g., vibration exposure, gait, and posture) [47] are associated with IVD degeneration or injury [2]. In particular, AF disruption is commonly linked to LBP and disability [12]. The healing process following AF injury includes inflammation, the recruitment of immune cells, cell proliferation, the formation of granulation tissue and matrix remodeling [12].…”

“…In particular, AF disruption is commonly linked to LBP and disability [12]. The healing process following AF injury includes inflammation, the recruitment of immune cells, cell proliferation, the formation of granulation tissue and matrix remodeling [12]. However, if initial inflammation is not resolved, it can become chronic and cause degeneration and pain [12].…”

“…Low back pain (LBP) is a condition with a lifetime prevalence of 84% and the primary cause of disability worldwide [10,11]. In particular, AF disruption is commonly linked to LBP and disability [12]. Current pharmacological treatments of LBP, such as anti-inflammatory drugs, do not take into account the mechanical aspect of the problem.…”

Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model

“…The healthy IVD has minimal vascularization, but increased vascularization is concurrent with degeneration and may result from AF disruption . Future studies in mouse could identify the phenotype and source of cells at the injury site …”

“…53 Future studies in mouse could identify the phenotype and source of cells at the injury site. 53,54 Interestingly, we observed higher Pfirrmann grade in Intact samples, which typically correlates with higher degeneration. 56 We also observed smaller disc height and larger disc height index for the Intact samples, likely due to naturally reduced disc height but possibly due to adjacent level effects.…”