Intervertebral Disc Degeneration and Regeneration: New Molecular Mechanisms and Therapeutics: Obstacles and Potential Breakthrough Technologies.

Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc's location, compartmentalization, hypovascularization and delicate physiological environment.

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease.

Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform.

Current Status of the Instructional Cues Provided by Notochordal Cells in Novel Disc Repair Strategies.

Numerous publications over the past 22 years, beginning with a seminal paper by Aguiar et al., have demonstrated the ability of notochordal cell-secreted factors to confer anabolic effects upon intervertebral disc (IVD) cells. Since this seminal paper, other scientific publications have demonstrated that notochordal cells secrete soluble factors that can induce anti-inflammatory, pro-anabolic and anti-cell death effects upon IVD nucleus pulposus (NP) cells in vitro and in vivo, direct human bone marrow-derived mesenchymal stem cells toward an IVD NP-like phenotype and repel neurite ingrowth.

Notochordal cell-derived conditioned medium protects human nucleus pulposus cells from stress-induced apoptosis.

Background Context: Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society.

Purpose: Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells.

Study Design/setting: This is an "in vitro" fundamental or basic science study.

The biological basis of degenerative disc disease: proteomic and biomechanical analysis of the canine intervertebral disc.

Introduction: In the present study, we sought to quantify and contrast the secretome and biomechanical properties of the non-chondrodystrophic (NCD) and chondrodystrophic (CD) canine intervertebral disc (IVD) nucleus pulposus (NP).

Methods: We used iTRAQ proteomic methods to quantify the secretome of both CD and NCD NP. Differential levels of proteins detected were further verified using immunohistochemistry, Western blotting, and proteoglycan extraction in order to evaluate the integrity of the small leucine-rich proteoglycans (SLRPs) decorin and biglycan.

Biologically based therapy for the intervertebral disk: who is the patient?

The intervertebral disk (IVD) is a fascinating and resilient tissue compartment given the myriad of functions that it performs as well as its unique anatomy. The IVD must tolerate immense loads, protect the spinal cord, and contribute considerable flexibility and strength to the spinal column. In addition, as a consequence of its anatomical and physiological configuration, a unique characteristic of the IVD is that it also provides a barrier to metastatic disease.