Breaking the Vicious Circle of Nucleus Pulposus Degeneration: Exploring Advanced Treatment Options for Lower Back Pain

Abstract

A major cause of disability in humans and dogs is lower back pain. Degeneration of the intervertebral disc stands out as prominent contributor to this. Degeneration typically starts in the core of the disc, the nucleus pulposus (NP), and is marked by an imbalance between extracellular matrix (ECM) synthesis and degradation. The lack of healthy NP cells impairs ECM restoration, exacerbates NP deterioration and ultimately leads to biomechanical failure of the disc. Current treatment options lack the potency required for successful NP stressing the need for advanced treatment strategies. This thesis contributes to this field by showing that improved in vitro methods support the phenotype of NP-derived cells and harmonization among labs accelerates both fundamental and translational research. Additionally, new insights into phenotypical markers improve the characterization of the heterogeneous cell population present in the young, matured and degenerated disc. From a translational perspective, the work advances treatment strategies that can halt or even reverse NP degeneration. It demonstrates that healthy ECM-inspired bioactive agents exert anabolic and anti-inflammatory effects on NP-cells. Furthermore, it reveals that the matrisome of healthy notochordal cell-rich NP tissue has the potency to support and instruct induced pluripotent stem cells as well as resident NP-cells in the harsh and degenerate disc environment. Altogether, the findings highlight that the combination of bioactive agents together with a suitable cell source seems promising to address important levels in the vicious circle of NP degeneration. This advanced treatment strategy shows the potential to functionally restore the disc, enabling sustained pain relief.