Cell Clusters Are Indicative of Stem Cell Activity in the Degenerate Intervertebral Disc: Can Their Properties Be Manipulated to Improve Intrinsic Repair of the Disc?

The aim of this study was to examine the complexity of the stem cell populations in the intervertebral disc (IVD) and understand their role in disc degeneration, with a view of determining whether the resident stem cells could be developed for therapeutic purposes to combat IVD degeneration. Stem cells have been isolated from disc and paradiscal tissues, including the notochord, annulus fibrosus (AF), nucleus pulposus (NP), cartilaginous endplate (CEP), ligamentum flavum, and vertebral body. Resident AF and NP cells are relatively sparsely distributed occurring as single or occasional doublet cells surrounded by an extensive extracellular matrix (ECM). Small clusters of 4-12 cells also occur close to annular lesions in experimental ovine and canine disc degeneration, these are indicative of an attempted repair response by resident stem cells. The rat IVD also has notochordal and peripheral cell populations in the outer AF, which express CS sulfation motifs (7-D-4, 4-C-3, 3-B-3[-]) characteristic of activated stem cells, the murine IVD also has a cell population in the outer AF adjacent to the vertebral growth plate with characteristics of a progenitor cell population. These have also been observed in rabbit, minipig, ovine, and human IVDs. Chondroid cell nests in the ovine NP may represent a progenitor/stem cell reserve. Such human chondroid cells express CS sulfation motifs (7-D-4, 4-C-3, 3-B-3[-]), cytokeratin-8 and 19, and CD cell surface markers typical of stem cells, including OCT3/4, CD105, CD90, STRO-1, NOTCH1, and JAGGED1. Similar stem cell populations are present in grade IV degenerate human IVDs. A greater understanding of the biology of this chondroid cell population may identify them as a therapeutic resource. A resident therapeutic cell type adapted to the demanding IVD environment may be advantageous in repair strategies.