Stem Cells and Intervertebral Disc Regeneration Overview-What They Can and Can't Do

Abstract

Background: Low back pain (LPB) is the main cause of disability worldwide with enormous socioeconomic burdens. A major cause of LBP is intervertebral disc degeneration (IDD): a chronic, progressive process associated with exhaustion of the resident cell population, tissue inflammation, degradation of the extracellular matrix and dehydration of the nucleus pulposus. Eventually, IDD may lead to serious sequelae including chronic LBP, disc herniation, segmental instability, and spinal stenosis, which may require invasive surgical interventions. However, no treatment is actually able to directly tackle IDD and hamper the degenerative process. In the last decade, the intradiscal injection of stem cells is raising as a promising approach to regenerate the intervertebral disc. This review aims to describe the rationale behind a regenerative stem cell therapy for IDD as well as the effect of stem cells following their implantation in the disc environment according to preclinical studies. Furthermore, actual clinical evidence and ongoing trials will be discussed, taking into account the future perspective and current limitations of this cutting-edge therapy.

Methods: A literature analysis was performed for this narrative review. A database search of PubMed, Scopus and ClinicalTrials.gov was conducted using "stem cells" combined with "intervertebral disc", "degeneration" and "regeneration" without exclusion based on publication date. Articles were firstly screened on a title-abstract basis and, subsequently, full-text were reviewed. Both preclinical and clinical studies have been included.

Results: The database search yielded recent publications from which the narrative review was completed.

Conclusions: Based on available evidence, intradiscal stem cell therapy has provided encouraging results in terms of regenerative effects and reduction of LBP. However, multicenter, prospective randomized trials are needed in order confirm the safety, efficacy and applicability of such a promising treatment.

Keywords: disc regeneration; intervertebral disc degeneration; intradiscal injection; mesenchymal stem cells; stem cell.

Figure 1

The main effects of stem cells following transplantation into the intervertebral disc. IVD, intervertebral disc; ECM, extracellular matrix; TNFα, tumor necrosis factor-α; IL, interleukin; IFN, interferon; MMP, matrix metalloproteinase. Created with BioRender.com.