Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy

Abstract

Background: Degenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management, which vary in the rate of success and also carry an increased risk of morbidity and mortality associated with the procedures. Several animal based studies and a few human pilot studies have demonstrated safety and suggest efficacy in the treatment of DDD with mesenchymal stem cells (MSCs). The use of bone marrow-derived MSCs for the treatment of DDD is promising and in the present study we report on the safety and efficacy findings from a registry based proof of concept study using a percutaneous intradiscal injection of cultured MSCs for the management of DDD with associated radicular symptoms.

Methods: Thirty-three patients with lower back pain and disc degeneration with a posterior disc bulge diagnosed on magnetic resonance imaging (MRI) met the inclusion criteria and were treated with culture-expanded, autologous, bone marrow-derived MSCs. Prospective registry data was obtained at multiple time intervals up to 6 years post-treatment. Collected outcomes included numeric pain score (NPS), a modified single assessment numeric evaluation (SANE) rating, functional rating index (FRI), measurement of the intervertebral disc posterior dimension, and adverse events.

Results: Three patients reported pain related to procedure that resolved. There were no serious adverse events (i.e. death, infection, or tumor) associated with the procedure. NPS change scores relative to baseline were significant at 3, 36, 48, 60, and 72 months post-treatment. The average modified SANE ratings showed a mean improvement of 60% at 3 years post-treatment. FRI post-treatment change score averages exceeded the minimal clinically important difference at all time points except 12 months. Twenty of the patients treated underwent post-treatment MRI and 85% had a reduction in disc bulge size, with an average reduction size of 23% post-treatment.

Conclusions: Patients treated with autologous cultured MSCs for lower back pain with radicular symptoms in the setting of DDD reported minor adverse events and significant improvements in pain, function, and overall subjective improvement through 6 years of follow-up. NCT03011398. A Clinical Registry of Orthobiologics Procedures. https://clinicaltrials.gov/ct2/show/NCT03011398?term=orthobiologics&rank=1.

Keywords: Autologous; Bone marrow; Culture-expanded stem cells; DDD; Degenerative disc disease; Intradiscal injection; MSC; Mesenchymal stem cells; Radicular pain; Regenerative medicine.

Fig. 1

Intradiscal approach targeting the L3-L4 IVD (circled area). A = superior articular process; B = needle

Fig. 2

Patient-reported improvement. Percent of patients reporting improvement categorized as better (modified SANE > 0% improvement) or no change (modified SANE = 0% improvement) at each post-treatment time point up to 6 years. Number of patients reporting at each time: 1 month (N = 5); 3 month (N = 19); 6 month (N = 15); 12 month (N = 13); 18 month (N = 12); 24 month (N = 7); 3 years (N = 10); 4 years (N = 13); 5 years (N = 10); 6 years (N = 9)

Fig. 3

Post-treatment reduction in disc bulge size by percentage threshold (N = 20). Patients at each threshold have obtained a reduction in disc bulge size of more than the percentage shown. For example, 85% of patients demonstrated a reduction of greater than 0%

Fig. 4

IVD herniation bulge measurements on MRI at pre-treatment compared to last post-treatment MRI shown by number of days after treatment. Lower values at the post-treatment time point indicates reduction in disc bulge size

Fig. 5

Comparison of disc bulge size on MRI. a Pre-treatment MRI, L5-S1, 4-30-2009; 6.5 mm posterior disc bulge. b 5 months post-treatment MRI, L5-S1, 1-5-2010; 3.9 mm posterior disc bulge