Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy

Abstract

Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.

Keywords: Stem cells; disc; disc cells; intervertebral disc degeneration.

Figure 1.

Anatomical configuration of human intervertebral disc from a sagittal perspective (a) with schematic demonstrating concentration gradient within actual disc in sagittal plane (b) and normalized concentration levels of specific metabolites demonstrating spatial relationship (c). Reproduced from Huang et al. with permission.

Figure 2.

Experimental design summary and strategy for testing scaffold-free tissue engineering and assessing regenerative potential. The scaffold-free approach involves culturing cells to produce ECM that will ultimately serve as the IVD implant. In vitro studies assess generated cartilaginous tissue while in vitro studies assess increases in cartilage tissue thickness.

Figure 3.

In vitro and in vivo investigation to understand scaffold-cell interactions, cell orientation and the cellular microenvironment and identify the optimal scaffold and conditions that satisfy the three biological components of the IVD.