Stromal Cell Derived Factor-1-Mediated Migration of Mesenchymal Stem Cells Enhances Collagen Type II Expression in Intervertebral Disc

Intervertebral disc (IVD) degeneration is characterized by an unbalanced cell catabolic/anabolic activity and cell death, resulting in the degradation of extracellular matrix components and water loss. Repopulating the IVD with new cells may help in recovering tissue homeostasis and reverting the degenerative process. In this study the regenerative potential of a hyaluronan (HA)-based chemoattractant delivery system able to recruit mesenchymal stem cells (MSCs) seeded on the cartilaginous endplate (CEP) of IVD was explored. A HA delivery system containing stromal cell derived factor-1 (SDF-1) (5 ng/mu L) (HAPSDF5) was injected in the cavity of nucleotomized bovine discs. Human MSCs (1 x 10(6)) were seeded on the opposite CEP and allowed to migrate for up to 21 days. Migration of fluorescently labelled MSCs from CEP toward the IVD was enhanced by HAPSDF5. Likewise, an increase in collagen type II was detected at earlier time points, whereas no effect on proteoglycan content within the nucleotomized IVDs was found. MSCs produced an increased concentration of pro-catabolic factors, such as interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). Overall, this study demonstrates that HAPSDF5 increased MSC recruitment, while the higher number of recruited cells partially contributed to accelerate matrix remodeling in nucleotomized IVDs.