Biologic Repair of the Intervertebral Disk

Abstract

The intervertebral disk is a pliant, multi-component tissue that performs a demanding biomechanical role in the spine. Disk degeneration is an inevitable consequence of aging, the rate of which depends on the combined effects of mechanical loading of the spine, impaired metabolite transport, disk-cell dysfunction, and other yet to be clarified inherited factors. Degeneration leads to the accumulation of matrix damage, biomechanical instability, and, in some individuals, pain. Biologically based therapies for intervertebral disk degeneration hold the promise of minimally invasive treatment and long-term symptom relief. The main categories of current approaches include bioactive proteins, genetic manipulation, and cell-based therapies. Injection of proteins, including growth and anti-inflammatory factors, can stimulate desirable responses in disk cells, but may have limited durability due to short protein half-life. Gene therapy can coax host cells to more sustainably secrete extracellular matrix, yet the clinical impact may be limited by the inherently low disk cellularity and potential safety concerns. The most promising therapies include delivery of cells that are primed to survive in the challenging disk environment and participate with host cells to rebuild matrix and down-regulate inflammation. For all approaches, therapy optimization is hampered by lack of ideal preclinical animal models, inadequate diagnostics for identifying patients, and sensitively monitoring outcomes, safety concerns, and, ultimately, development costs.

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