While chronic lower back pain interferes with simple activities of daily life such as sitting, standing, and walking, it also severely impacts one’s ability to work. Current first-line treatments are diverse and range from lifestyle changes to pain medication, with surgery as a last resort. However, surgery is known to have mixed results regarding improvement of symptoms and could lead to other complications. Because of this, available treatment options heavily focus on reducing pain to prevent surgery. This begs the question: is there a better way?
In this review, Bach and colleagues across the globe explore the relatively overlooked notochordal cells and their potential to treat lower back pain. These cells come from an early formation of the embryo’s backbone and reside within the developing intervertebral disc, the cushion between the vertebrae. They make the point that notochordal cells have regenerative and anti-inflammatory properties that may address an unmet need among current treatment options around lower back pain. Importantly, the authors also explore future directions around this new and exciting area of research!
Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration
Authors: Frances C. Bach, Deepani W. Poramba-Liyanage, Frank M. Riemers, Jerome Guicheux, Anne Camus, James C. Iatridis, Danny Chan, Keita Ito, Christine L. Le Maitre and Marianna A. Tryfonidou
First published: 14 March 2022
Abstract: Chronic low back pain is the number one cause of years lived with disability. In about 40% of patients, chronic lower back pain is related to intervertebral disc (IVD) degeneration. The standard-of-care focuses on symptomatic relief, while surgery is the last resort. Emerging therapeutic strategies target the underlying cause of IVD degeneration and increasingly focus on the relatively overlooked notochordal cells (NCs). NCs are derived from the notochord and once the notochord regresses they remain in the core of the developing IVD, the nucleus pulposus. The large vacuolated NCs rapidly decline after birth and are replaced by the smaller nucleus pulposus cells with maturation, ageing, and degeneration. Here, we provide an update on the journey of NCs and discuss the cell markers and tools that can be used to study their fate and regenerative capacity. We review the therapeutic potential of NCs for the treatment of IVD-related lower back pain and outline important future directions in this area. Promising studies indicate that NCs and their secretome exerts regenerative effects, via increased proliferation, extracellular matrix production, and anti-inflammatory effects. Reports on NC-like cells derived from embryonic- or induced pluripotent-stem cells claim to have successfully generated NC-like cells but did not compare them with native NCs for phenotypic markers or in terms of their regenerative capacity. Altogether, this is an emerging and active field of research with exciting possibilities. NC-based studies demonstrate that cues from developmental biology can pave the path for future clinical therapies focused on regenerating the diseased IVD.
Funding information: This manuscript has received funding from the European Union’s Horizon 2020 research and innovation program (iPSpine; grant agreement number 825925, with FB, DWP-L, FR, JG, AC, DC, KI, CM, and MT involved). MT, DWP-L, FR, and FB received funding from the Dutch Arthritis Society (LLP22). JG received funding from the French National Agency (ANR REMEDIV project; ANR14-CE16-0017) the FRM (Bioingenierie DBS20131128442) and the AO foundation (S-12-14G). AC received funding from the French Society of Rheumatology (Spherodisc). DC received funding from the Research Council of Hong Kong (E-HKU703/18).