The intervertebral disk (IVD) is a fascinating and resilient tissue compartment given the myriad of functions that it performs as well as its unique anatomy. The IVD must tolerate immense loads, protect the spinal cord, and contribute considerable flexibility and strength to the spinal column. In addition, as a consequence of its anatomical and physiological configuration, a unique characteristic of the IVD is that it also provides a barrier to metastatic disease. However, when injured and/or the subject of significant degenerative change, the IVD can be the source of substantial pain and disability. Considerable efforts have been made over the past several decades with respect to regenerating or at least modulating degenerative changes affecting the IVD through the use of many biological agents such as growth factors, hydrogels, and the use of plant sterols and even spices common to Ayurvedic medicine. More recently stem/progenitor and autologous chondrocytes have been used mostly in animal models of disk disease but also a few trials involving humans. At the end of the day if biological therapies are to offer benefit to the patient, the outcomes must be improved function and/or less pain and also must be improvements upon measures that are already in clinical practice. Here some of the challenges posed by the degenerative IVD and a summary of some of the regenerative attempts both in vitro and in vivo are discussed within the context of the vital question: "Who is the patient?"
Keywords: biological therapy; growth factors; intervertebral disk; regenerative medicine; stem cells.