An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype. © 2014 The Author(s)

Exploiting notochord cells for stem cell-based regeneration of the intervertebral disc

The nucleus pulposus is an avascular and aneural tissue that has significant influence on the homeostasis and overall function of the intervertebral disc. The nucleus pulposus is comprised of a heterogeneous population of cells including large notochord cells and smaller chondrocyte-like cells. Loss of notochord cells has been correlated with the pathogenesis of disc degeneration and consequently, it has been hypothesized that regeneration of the disc could be mediated by notochord cells. Attempts to grow and expand notochord cells in vitro have thus far been limited by cell availability and ineffective culturing methodologies. As a result, co-culturing techniques have been developed in order to exploit notochord-derived signals for the differentiation of proliferative mesenchymal stem cells. A recent study by Korecki et al. has demonstrated that notochord cell conditioned medium has the ability to differentiate mesenchymal stem cells toward a nucleus pulposus-like fate, producing high levels of glycosaminoglycans and type III collagen. These findings suggest that growth factors and other soluble proteins may be able to stimulate endogenous IVD tissue maintenance in vivo. While this study advances our understanding of intervertebral disc cell-cell interactions, limitations remain in our ability to determine the phenotype of terminally differentiated cells within the nucleus pulposus (ie mature notochord cells) and therefore assess the relevance of differentiated mesenchymal stem cells for disc regeneration. In order for the field to progress, elucidation of the notochord phenotype remains of utmost importance