Revealing the presence of lymphatic vessels within intervertebral discs: Novel insights into disc degeneration
The intervertebral disc (IVD) is a crucial fibrocartilaginous structure that connects adjacent vertebrae. It plays a fundamental role in maintaining spinal stability and absorbing mechanical stress. Each disc is composed of three parts: the inner nucleus pulposus (NP), the outer annulus fibrosus (AF), and the superior and inferior cartilage endplates (CEPs). Degeneration of IVDs is a primary contributor to various spinal disorders, such as cervical spondylosis, low back pain, and lumbar disc herniation, all of which lead to a significant reduction in the quality of life of patients and impose a substantial economic burden. In China, IVD degeneration (IVDD) is the third most common chronic disease following hypertension and diabetes, highlighting the widespread impact of IVDD on public health.
Non-degenerated adult IVDs are devoid of a vascular system within their internal structure; that is, they lack both blood and lymphatic vessels. Nutrient supply to these discs primarily relies on diffusion from the capillaries into the CEPs and the outer layers of the AF. This limited nutrient exchange significantly restricts the self-repair and self-regenerative abilities of IVDs, making them more vulnerable to degeneration. The absence of vascular and lymphatic systems in IVDs is considered a major factor contributing to the pathogenesis of IVDD.
A hallmark of IVDD is the formation of microvessels within the degenerated disc tissue, particularly in the AF. Although the ingrowth of microvessels may temporarily provide a compensatory nutrient supply to the disc, it may exacerbate inflammatory cell infiltration, intensifying the inflammatory response and accelerating disc degeneration. The reason for the failure of clearance of these cells remains unknown in the context of IVDD.
Although the presence of blood vessels in degenerated discs has been extensively reported, studies investigating the presence and role of lymphatic vessels in IVDs are relatively limited. As integral components of the vascular system, lymphatic vessels are essential for maintaining tissue fluid homeostasis, removing metabolic waste, and regulating immune responses. In other tissues, lymphangiogenesis has been shown to support tissue repair by facilitating the clearance of excess interstitial fluid and immune cells. Therefore, lymphatic vessels may play a similar role in maintaining disc health and mitigating degeneration.
In this study, we demonstrated the presence of lymphatic vessels in the AF of healthy discs, contradicting the conventional belief that non-degenerated adult IVDs are devoid of a vascular system. We used spatial transcriptomic analysis and immunohistochemistry (IHC) and immunofluorescence staining to provide evidence of lymphatic vessels within the AF. Furthermore, we found that an increase in the number of blood vessels in degenerated discs significantly decreased the number of lymphatic vessels. These findings suggest that lymphatic vessels play a crucial role in regulating the nutritional metabolism and immune microenvironment of IVDs, offering novel insights into the mechanisms underlying IVDD progression. Altogether, the results of this study suggest that regulating the lymphatic system is a promising therapeutic strategy for IVDD.
