1. 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
- Author
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Soo-Hong Lee, Inbo Han, Hemant Kumar, Doo-Hoe Ha, Kyoung-Tae Kim, Chung-Hun Kim, Jeong Hyun Shim, Seil Sohn, Tae-Keun Ahn, Jun Hee Park, Alexander E. Ropper, Eun-Jong Lee, and Devang K. Thakor
- Subjects
Male ,0301 basic medicine ,Nucleus pulposus ,Medicine (miscellaneous) ,Phases of clinical research ,Intervertebral Disc Degeneration ,Injections, Intralesional ,Cell therapy ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,lcsh:QD415-436 ,Intervertebral Disc ,Pain Measurement ,lcsh:R5-920 ,education.field_of_study ,Cell Differentiation ,Middle Aged ,Low back pain ,Oswestry Disability Index ,Treatment Outcome ,Adipose Tissue ,Tolerability ,Molecular Medicine ,Female ,Patient Safety ,medicine.symptom ,lcsh:Medicine (General) ,Adult ,medicine.medical_specialty ,Visual analogue scale ,Hyaluronic acid ,Population ,Mesenchymal Stem Cell Transplantation ,Transplantation, Autologous ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,lcsh:Biochemistry ,03 medical and health sciences ,Adipose-derived mesenchymal stem cells ,medicine ,Humans ,Adverse effect ,education ,business.industry ,Research ,Water ,Mesenchymal Stem Cells ,Cell Biology ,Surgery ,030104 developmental biology ,Chronic Disease ,business ,Low Back Pain ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Adipose 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. Methods We 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. Results No 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. Conclusions Combined 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 registration ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.
- Published
- 2017