Barriers to mesenchymal stromal cells for low back pain

Abstract

Intervertebral disc degeneration is the main cause of low back pain. In the past 20 years, the injection of mesenchymal stromal cells (MSCs) into the nucleus pulposus of the degenerative disc has become the main approach for the treatment of low back pain. Despite the progress made in this field, there are still many barriers to overcome. First, intervertebral disc is a highly complex load-bearing composite tissue composed of annulus fibrosus, nucleus pulposus and cartilaginous endplates. Any structural damage will change its overall biomechanical function, thereby causing progressive degeneration of the entire intervertebral disc. Therefore, MSC-based treatment strategies should not only target the degenerated nucleus pulposus but also include degenerated annulus fibrosus or cartilaginous endplates. Second, to date, there has been relatively little research on the basic biology of annulus fibrosus and cartilaginous endplates, although their pathological changes such as annular tears or fissures, Modic changes, or Schmorl's nodes are more commonly associated with low back pain. Given the high complexity of the structure and composition of the annulus fibrosus and cartilaginous endplates, it remains an open question whether any regeneration techniques are available to achieve their restorative regeneration. Finally, due to the harsh microenvironment of the degenerated intervertebral disc, the delivered MSCs die quickly. Taken together, current MSC-based regenerative medicine therapies to regenerate the entire disc complex by targeting the degenerated nucleus pulposus alone are unlikely to be successful.

Keywords: Editorial; Intervertebral disc degeneration; Low back pain; Mesenchymal stromal cells; Nucleus pulposus; Regenerative medicine.

Figure 1

Annulus fibrosus structure. Annulus fibrosus (AF) is composed of 15-25 concentric lamellar layers with oblique collagen fibers in alternating directions lying parallel within each lamella. From the edge of the disc inward through the annulus, the angle-ply fiber orientation (θ) decreases from ± 62° from the vertical axis to ± 45° in a linear manner. From the outer to inner AF regions, glycosaminoglycan increases from 3% to 8% per wet weight, while the ratio of type I collagen to type II collagen decreases. The inner AF mainly contains rounded fibrocartilage cells, and the outer AF mainly contains elongated fibroblast-like cells, while other cell types located in or near the AF include peripheral cells, interlamellar cells, and stem/progenitor cells.

Figure 2

Action mechanisms underlying mesenchymal stromal cell-mediated disc repair. IDO: Indoleamine 2,3-dioxygenase; IL: Interleukin; MVs: Microvesicles; TGF-: Transforming growth factor-beta.