Biological challenges for regeneration of the degenerated disc using cellular therapies

Interest in the biology of the intervertebral disc has grown significantly over the past 2 decades, driven mainly by studies aimed at developing biological therapies for repairing degenerate discs (Alini et al. 2002, Sakai and Grad 2015). Most interest has focused on cellular therapies, where cells, capable of synthesizing appropriate disc tissue, are implanted into the damaged tissue to replace resident cells that have died or have acquired a degenerative phenotype. This appears to be an attractive strategy, and has led to a significant increase in information about disc cellular biology. It follows the approach used clinically for repairing damaged cartilage (Hunziker et al. 2015); however, cell therapy for the disc faces more obstacles than that for cartilage repair and has not yet entered routine clinical practice. In this review, we discuss some of the challenges in successful cellular repair of the disc. We first review the function, organization, and composition of a normal disc, outline the changes that occur in degeneration, and consider how these might influence function. We then summarize cell therapy approaches to repairing the disc in relation to the choice of cells and cell support. We outline the challenges facing the implanted cells in the degenerate disc, and ask whether these therapies can be evaluated in animal models. Finally, we outline the important, but often neglected, problem of patient selection.