title: Advancing the cellular and molecular therapy for intervertebral disc disease.
abstract: The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.
authors.affiliation: Department of Orthopaedic Surgery, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan; Collaborative Research Partner Annulus Fibrosus Repair Program, AO Foundation, Davos, Switzerland. Electronic address: daisakai@is.icc.u-tokai.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakai
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland; Collaborative Research Partner Annulus Fibrosus Repair Program, AO Foundation, Davos, Switzerland. Electronic address: sibylle.grad@aofoundation.org.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
mesh_terms: D001685:Biological Factors / Q000008:administration & dosage*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000628:therapy*; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D001685:Biological Factors
keywords: Cell therapy; Homeostasis; Homing; Intervertebral disc degeneration; Intra-cellular pathways; Niche; Progenitor cells; Target