1. 2022;25;193-207Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial
   Prospective Study
   Nikhil Grandhi, ., Laxmaiah Manchikanti, MD, Zaynab Syed, ., Divit Jain, ., Meghana Ganjam, ., Pavan Yerramsetty, MD, Zaid Syed, ., Navneet Boddu, MD, Sachi Bhati, ., Vivek Manocha, MD, Kwadwo Boachie-Adjei, BS, CPH, Jessica Herrera, BS, Ryan Dregalla, PhD, Sairam Atluri, MD, and Matthew B. Murphy, PhD.

BACKGROUND: Regenerative medicine interventions are applied to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous/allogenic biologics and it continues to expand. The anti-inflammatory, immunomodulatory, and regenerative properties of bone marrow mesenchymal stem cells (BM-MSCs), and investigation into their therapeutic efficacy and safety in patients with severe chronic low back pain, have not been demonstrated in controlled studies. Multiple pain generators have been hypothesized to be responsible in severe spinal degeneration and it is difficult to identify a single pain generator; consequently, resulting in inadequate therapeutic results.

OBJECTIVES: The study was undertaken to evaluate the effectiveness of autologous bone marrow MSCs in the treatment of chronic low back pain due to severe lumbar spinal degeneration with involvement of multiple structures.

STUDY DESIGN: Prospective, open-label, nonrandomized, parallel-controlled, 2-arm exploratory study.

SETTING: A private, specialized, interventional pain management and regenerative medicine clinic.

METHODS: The treatment group patients received a one-time bone marrow concentrate injection into spinal structures (i.e., discs, facets, spinal nerves, and sacroiliac joints), along with conventional treatment, whereas, the control group received conventional treatment with nonsteroid anti-inflammatory drugs, over-the-counter drugs, structured exercise programs, physical therapy, spinal injections and opioids, etc., as indicated.

Outcomes Assessment: Outcomes were assessed utilizing multiple instruments, including the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS-11), EuroQOL 5-Dimensional Questionnaire (EQ-5D-3L), Global Mental Health (GMH), and Global Physical Health (GPH). Multiple outcomes were assessed with primary outcomes being minimal clinically important differences (MCID) in ODI scores between the groups and/or a 2-point reduction in pain scores.

In the study group, total nucleated cells, colony forming units-fibroblast, CD34-positive  cell numbers and platelets were also recorded, along with post-procedure magnetic resonance imaging changes. Outcomes were assessed at 1, 3, 6, and 12 months.

RESULTS: Significant improvement was achieved in functional status measured by ODI, pain relief measured by NRS-11, and other parameters measured by EQ-5D-3L, GMH, and GPH, in the study group relative to the control group at all time periods. The results showed significant improvements at 12-month follow-up with 67% of the patients in the study group achieving MCID utilizing ODI when compared to 8% in the control group. Greater than 2-point pain reduction was seen in 74% of the patients at 3 months, 66% of the patients at 6 months, and 56% of the patients at 12 months. Both MCID and pain relief of 2 points were significantly different compared to the control group. Opioid use decreased in the investigational group, whereas, there was a slight increase in the control group. Age, gender, opioid use, and body mass index did not affect the outcomes in the stem cell group.

LIMITATIONS: Single center, nonrandomized study.

CONCLUSIONS: The first available controlled study utilizing BM-MSCs in severe degenerative spinal disease with interventions into multiple structures simultaneously, including disc, facet joints, nerve roots, and sacroiliac joint based on symptomatology, showed promising results.

KEY WORDS: Low back pain, spinal degeneration, disc, facet joint, sacroiliac joint, regenerative medicine, autologous, bone marrow mesenchymal stem cells