Current Understanding of Safety and Efficacy of Stem Cell Therapy for Discogenic Pain: A Systematic Review of Human Studies
Background: Low back pain is the leading cause of disability in the developed world and places a heavy cost burden on healthcare. One of the leading causes of low back pain is intervertebral disc (IVD) degeneration. Human clinical trials examining the safety and efficacy of mesenchymal stem cell (MSC) therapy in the treatment of pain due to IVD degeneration have recently been published and larger randomized phase 2 trials are ongoing. However they are limited by small sample size, heterogeneous trial designs, and conflicting outcomes.
Objective: To summarize the current human trials and feasibility studies involving mesenchymal stem cell (MSC) therapy for treatment of discogenic pain and provide a research base for future randomized controlled trials (RCTs) involving MSC transplantation in the treatment of patients with discogenic pain due to IVD degeneration.
Methods: A search of Ovid databases and Clinicaltrials.gov was conducted from inception through July 2016. We included human clinical trials and case reports that evaluated treatment with injected MSCs for patients with discogenic back pain.
Results: The initial search in Ovid databases using the selected search terms identified 408 results, of which eleven were included in this review based on selection criteria. In the six completed studies involving intradiscal stem cell injections, improvement in pain, function, and T2 weighted MRI intensity of the nucleus pulposus were reported. Currently active clinical trials focus on establishing safety, tolerability, and efficacy with respect to injected MSCs for discogenic pain.
Conclusions: MSC transplantation is theorized to facilitate regeneration of the IVD by differentiation to a nucleus pulposus (NP) cell-like phenotype or through stimulation of endogenous NP cells in the IVD. The current literature aims to link the proposed mechanisms behind MSC transplantation with improvement in back pain and function, but there is a lack of sufficient high quality studies to demonstrate whether disc regeneration indeed results from MSC implantation. The results of this systematic review suggest that human clinical trials may bear out what the research to date has proposed regarding the mechanisms of IVD regeneration via MSC transplantation, especially if outcomes that elucidate to what extent disc regeneration may have actually taken place can be measured. Although pain and functional benefit have been reported in association with stem cell therapy, longer-term safety studies and more RCTs are needed to examine the safety and efficacy of stem cell therapy for discogenic pain.