Nucleus pulposus cell regeneration by notochordal cell matrix as treatment for intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IVDD) has been indicated as one of the main causes of low back pain, a major health problem in both humans and dogs. Current treatments lack long term efficacy and focus on the symptoms, rather than the repair of the degenerated intervertebral disc. New regenerative therapies could repopulate the nucleus pulposus (NP) and stimulate the resident nucleus pulposus cells (NPCs). Notochordal cell matrix (NCM) is a new, promising medium with regenerative potential. The goal of this study is to determine the effect of NCM on the regeneration of human and canine nucleus pulposus cells (NPCs) derived from degenerated intervertebral discs (IVDs). Additionally, we want to find out whether the decellularization process influences the regenerative capacity of the NCM. NPCs from degenerated IVDs (Thompson grade II and III) of 6 chondrodystrophic canine and 6 human donors were cultured in base culture medium, transforming growth factor beta 1, NCM (2 or 10 mg/ml) or non-decellularized NCM (10 mg/ml). Afterwards, qPCR amplification, quantitative GAG and DNA measurements and 4 types of histological staining were performed. This study showed a decrease in apoptosis and matrix degradation and an increase in cell proliferation and matrix production (particularly GAGs) in NCM-treated samples. Non-decellularized NCM had significantly higher GAG levels, indicating the decellularization process influenced the regenerative potential of the NCM. Taken together, the results of this study demonstrate the regenerative potential of NCM for NPCs in degenerated IVDs, especially in dogs.