Abstract
Degeneration of intervertebral disc (IVD) Nucleus Pulposus (NP) is a major cause of low back pain (LBP). Healthy NP contains two cell types: notochordal cells (NTC) and nucleopulpocytes (NPCytes). While NTC are embryonic notochord derived cells that are regarded as the resident stem cells of NP, NPCytes are considered the mature NP cells responsible for extracellular matrix (ECM) synthesis. During IVD aging, some still unknown cues drive NTC disappearance. This loss of NTC alters their dialog with NPCytes thereby jeopardizing cell viability and ECM homeostasis, which in turn drives NP degeneration. In this context, NP regeneration by re-establishing this NTC/NPCytes dialog has been contemplated with clinical interest. We will first share our view of the mesenchymal stem cells (MSC)-based therapies that have been preclinically and clinically assessed in LBP. We will then comment on the biomaterial-assisted MSC therapies that recently enter the scene of IVD regeneration. Finally, we will present our REMEDIV project that aims at developing a NP substitute containing stem cells-derived NPCytes and NTC within an injectable hydrogel. We will share our results regarding the generation of NPCytes from adipose-derived MSC and our recent unpublished evidences that human induced-pluripotent stem cells can be differentiated into NTC. Finally, we will consider our ability to transplant these regenerative cells using hydrogels in various animal models. Whether this concept could open new therapeutic windows in the management of discogenic low back pain will finally be discussed.
