• Daisuke Sakai and Sibylle Grad.
• 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.
• Adv. Drug Deliv. Rev. 2015 Apr 1; 84: 159-71.

AbstractThe 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.Copyright © 2014 Elsevier B.V. All rights reserved.

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