Preconditioning Mesenchymal Stem Cells to Enhance Performance in the Degenerate Nucleus Pulposus

Degeneration of the lumbar intervertebral discs is a leading cause of low back pain, a condition that affects a substantial proportion of the global population. The earliest degenerative changes typically manifest in the central nucleus pulposus (NP) region of the disc and are characterized by elevated local inflammation and a cell-mediated reduction in proteoglycan content and transition to a fibrotic extracellular matrix. The application of adult mesenchymal stem cells (MSCs) to arrest and reverse degenerative changes in the NP has received significant interest due to the availability and superior safety profile of these cells compared with other therapeutic cell types. Preclinically and clinically, however, the efficacy of MSC-based disc treatments is mixed, due in part to the limited ability of these cells to survive and function within the degenerate NP microenvironment. A potential strategy to improve the in vivo survival and anabolic performance of MSCs in the degenerate NP is preconditioning prior to implantation using a variety of biochemical and biophysical stimuli. In this review, we present an overview of existing techniques used for preconditioning MSCs to enhance their therapeutic performance in the degenerate NP. We outline respective advantages and challenges associated with each of these techniques and provide recommendations for their further refinement.