Notochordal and Mesendoderm Progenitor Cells as Potential Cell Sources for Disc Degeneration-Associated Back Pain

Conflicts of Interest: None Sources of Funding: Funded by Horizon 2020 Introduction During disc degeneration the nucleus pulposus (NP) is broken down and loses function. It has been proposed that notochordal (NC) cells, embryonic IVD cells, could be utilised for mediating regeneration as they can increase anti-catabolic factors and matrix synthesis. This study investigated the co-culture of NC cells with degenerate NP cells to determine the anti-catabolic effects NC cells potentially provide. Also, due to the lack of availability of NC cells as a viable treatment strategy, we also investigated the effects of induced pluripotent stem cell-generated mesendoderm progenitor cell (MEPC–precursors to NC cells) co-culture with human NP tissue, to determine the potential regenerative capacity of MEPCs. Methods Porcine NCs (pNC) and human NP cells were encapsulated separately in 3D alginate beads and co-cultured in conditions mimicking the healthy and degenerate disc. Subsequently, iPSCs were differentiated into MEPCs and injected into degenerate human NP tissue. Viability, gene expression, protein expression and secretion were investigated. Results No significant differences were seen in phenotypic marker expression in NCs cultured in any media. Co-culture of NP cells with pNC cells showed significantly reduced production of catabolic factors. Following culture, MEPCs were identified within NP tissue, their viability was maintained and the production of catabolic factors decreased. Conclusions Results indicated that within the degenerate IVD environment NCs retain their phenotype and can modulate the production of catabolic proteins from degenerate NP cells when co-cultured together. The generation of MEPC precursors from iPSCs can enable the production of NC-like cells, whereas previously the use of NC cells for IVD regeneration has not been considered due to their lack of availability.