Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study

Abstract

BackgroundAdipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP.MethodsWe performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year.ResultsNo patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI.ConclusionsCombined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population.Trial registrationClinicalTrials.gov NCT02338271. Registered 7 January 2015.

Differential Effector Response of Amnion‐ and Adipose‐Derived Mesenchymal Stem Cells to Inflammation; Implications for Intradiscal Therapy

“…These findings have prompted clinical trials evaluating the safety and efficacy of intradiscal administration of MSCs to attenuate progression of IVD degeneration. These trials have yielded improved pain and functional outcomes in patients with Pfirrmann grade II‐V IVD degeneration . However, identification of an MSC source which demonstrates optimal therapeutic outcomes within the complex pathological environment of the IVD has yet to be defined …”

Photopolymerizable biogel scaffold seeded with mesenchymal stem cells: safety and efficacy evaluation of novel treatment for intervertebral disc degeneration

“…One recent study by Centeno et al examined percutaneous injection of MSCs into in vivo human lumbar discs with hernation of the NP; they described a low complication rate, clinical improvement and decrease in the size of disc herniation on long term follow up . When looking at intradiscal injection of MSCs and hyaluronic acid scaffold in a clinical trial of 10 patients, Kumar et al reported no adverse events and improved clinical outcome measures . Of the improved patients, 50% had increased water content within the disc at long‐term follow up, though no changes were noted in radiographic measures of disc degeneration.…”

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

“…(121,122) With regards to MSC therapy, feasibility and safety have been suggested in pilot clinical studies among chronic back pain patients. (123)(124)(125) Analgesic effect, functional improvement, and increased water content by MSC injection therapy have also been reported, although there was no effect on recovering disc height. (123)(124)(125) Furthermore, improvement may be restricted to a group of responders.…”

“…(123)(124)(125) Analgesic effect, functional improvement, and increased water content by MSC injection therapy have also been reported, although there was no effect on recovering disc height. (123)(124)(125) Furthermore, improvement may be restricted to a group of responders. (124,125) Optimization of indication (to distinguish responders and nonresponders), cellsource, cell concentration, and scaffold type are needed, as are larger-scale clinical trials to show long-term safety and efficacy.…”