Development and Degeneration of the Intervertebral Disc—Insights from Across Species

Abstract

Back pain caused by intervertebral disc (IVD) degeneration has a major socio-economic impact in humans, yet historically has received minimal attention in species other than humans, mice and dogs. However, a general growing interest in this unique organ prompted the expansion of IVD research in rats, rabbits, cats, horses, monkeys, and cows, further illuminating the complex nature of the organ in both healthy and degenerative states. Application of recent biotechnological advancements, including single cell RNA sequencing and complex data analysis methods has begun to explain the shifting inflammatory signaling, variation in cellular subpopulations, differential gene expression, mechanical loading, and metabolic stresses which contribute to age and stress related degeneration of the IVD. This increase in IVD research across species introduces a need for chronicling IVD advancements and tissue biomarkers both within and between species. Here we provide a comprehensive review of recent single cell RNA sequencing data alongside existing case reports and histo/morphological data to highlight the cellular complexity and metabolic challenges of this unique organ that is of structural importance for all vertebrates.

Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects

“…While often effective, these therapies have their limitations as they are based upon the patient's symptoms, with an emphasis on correcting the patient's pain. These therapies therefore lack the ability to reverse the underlying degenerative process or restore the biomechanical function of this unique and important tissue [4,8]. As the incidence of IVD degeneration has increased, the pathophysiology of this disease has been increasingly studied, and various treatments have been developed.…”

“…As a result, this degenerative process results in loss of the nucleus pulposus, loss in disc height, and subsequent disc bulging [17]. This weakened structure can lead to a variety of symptomatic pathologic conditions including disc herniations, spinal stenosis, spinal instability, and deformity [4,17].…”

“…Notably, IVD degeneration is generally thought to begin with changes in the NP with a host of well-studied changes in ECM elements [3]. While also caused by other numerous different pathoanatomic findings, degeneration of the intervertebral disc's annulus fibrosus, followed by extrusion of the nucleus pulposus material and subsequent compression of nerve fibers, is a leading cause of this lower back pain [4]. Degeneration of IVD begins with an increase in proteolysis and inflammatory cytokines, while aging and alterations are associated with the breakdown of extracellular matrix, particularly aggrecan and collagen.…”

“…Currently, both surgical and non-surgical therapies are the mainstays of treatment and include physical therapy, anti-inflammatories, corticosteroids, and surgery to arthrodesis or replace the symptomatic IVD. However, while effective, these therapies have their limitations as they are largely ablative, with an emphasis on reducing the patient's pain and dysfunction, and are neither able to reverse the IVD degenerative process nor restore the mechanical and physiologic function of the IVD [4,8].…”

“…Many hydrogels are readily compatible with biological tissues and do not elicit major immune responses. Additionally, because of their high water content, hydrogels can also offer a suitable aqueous environment that promotes the proliferation and activity of IVD cells [4][5][6]. These biomaterials also have a variety of tunable biochemical and biomechanical properties, such as shear-thinning behavior, biodegradability, ECM biomimicry, and physiochemical properties that make them an attractive, appropriate, and functional tool to address intervertebral disc degeneration [11].…”