Low-dose Mesenchymal Stem Cell Therapy for Discogenic Pain: Safety and Efficacy Results From a 1-year Feasibility Study

Figures & data

Figure 1. A flow chart highlighting the study design of this trial.

Table 1. Eligibility criteria for participants.

Key inclusion criteria
1. Chronic LBP of discogenic origin for at least six months
2. LBP ≥ 5/10 on numeric pain rating scale at enrolment
3. Aged 18 years or older who have previously had three months of unsuccessful conservative back pain care, including, for example, medications (anti-inflammatories, analgesics, muscle relaxants), massage, acupuncture, chiropractic manipulations, activity modification, home directed lumbar exercise programs
4. If present, leg pain <LBP, and of nociceptive not radicular type
5. MRI findings:     a) One level disc degradation without disc space height loss of more than 50% +/- Modic type I or II changes at the same level     b) May include contained disc herniations ≤3 mm protrusion with no imaging evidence of neurological compression
Key exclusion criteria
1. Pregnancy or breast feeding (accepted contra-indication as no safety data on this population).
2. Discogram positive patients with a grade 5 annular tear (it is not known what the effect of dilution will have when the cells penetrate through the annulus fibrosus into the epidural space)
3. A prior history of cancer or other malignant condition, or an atypical chronic pain syndrome
4. A history of epidural steroid injections within eight weeks prior to treatment injection
5. Previous surgery at the symptomatic disc that has altered the structure of the target disc level (e.g. discectomy, laminectomy, foraminotomy, fusion, intradiscal electrothermal therapy, intradiscal radiofrequency, thermocoagulation)
6. A current diagnosis of bleeding disorders and/or taking prescribed anti-coagulants that cannot be ceased
7. A history of allergy to any substances used within the treatments

LBP: Low back pain.

Table 2. Average cell count and viability confirmed using a muse cell analyzer.

	Baseline ADMSC injection (n = 9)		6-month ADMSC injection (n = 5)
	Cell count (millions)	Cell viability (%)	Cell count (millions)	Cell viability (%)
Mean	10.9	96.6	10.2	96.8
SD	0.99	1.17	0.4	0.98

ADMSC: Adipose-derived mesenchymal stem cell; SD: Standard deviation.

Table 3. Tools used for the evaluation of outcome measures.

Outcome measures	Measurement point (months)
Primary outcome measure
NPRS	0, 1, 3, 6, 9, 12
Secondary outcome measures
DASS21	0, 1, 3, 6, 9, 12
ODI	0, 1, 3, 6, 9, 12
Standing, sitting and walking tolerances	0, 1, 3, 6, 9, 12
EQ-5D-3L	0, 1, 3, 6, 9, 12
Change to employment capability	0, 1, 3, 6, 9, 12
Patient satisfaction	1, 3, 6, 9, 12
PGIC	1, 3, 6, 9, 12
MRI	0, 12

DASS21: Depression, anxiety and stress scale; NPRS: Numeric pain rating scale; ODI: Oswestry disability index; PGIC: Patient global impression of change.

Table 4. Participant demographics.

Gender, male vs female	56 vs 44
Age (years)	40.1 (10.3)
Height (m)	1.7 (0.1)
Weight (kg)	75.3 (17.6)
BMI (kg/m^2)	25.4 (3.1)

Standard deviation in brackets.

Figure 2. Tornado plots showing percentage improvement in numeric pain rating scale scores for each participant.

(A) Average pain scores at 6 months. (B) Average pain scores at 12 months. (C) Most severe pain at 6 months. (D) Most severe pain at 12 months.

Figure 3. Changes to duration of standing, sitting and walking tolerance after 12 months.

Figure 4. ODI results showing percentage improvement in functional outcomes for each participant.

(A) 6 months. (B) 12 months.

Figure 5. ODI results showing clinical outcomes at baseline, 6 and 12 months.

Figure 6. Percentage of participants reporting each category in functional outcomes (EQ-5D-3L) at baseline, 6 and 12 months.

(A) Usual activities. (B) Self-care.

Figure 7. 12-month data showing participant satisfaction and patient global impression of change data.

(A) Categorical PGIC data. (B) Participant satisfaction survey.

PGIC: Patient global impression of change.

Table 5. Baseline and 12-month MRI findings.

Pt no.	Treatment disc	Baseline MRI findings	12–month MRI findings
02	L5/S1	Desiccated disc with shallow disc protrusion Hyperintense posterior peripheral zone (annular fissure) Normal disc height	No changes in disc height No progression of shallow disc protrusion Hyperintense posterior peripheral zone (annular fissure) has resolved
03	L5/S1	Narrowed desiccated disc Mild broad based disc protrusion Endplate cortical irregularity with type 2 Modic changes	No changes in disc height or disc desiccation No change in disc protrusion No change in Modic 2 endplate changes
04	L5/S1	Desiccated disc with moderate to severe narrowing at its right lateral margin. Modic I endplate degenerative change. Disc protrusion, mild disc bulge with small posterior annular tear	No changes in disc height No progression of endplate degenerative changes No change in small posterior annular tear
07	L5/S1	Narrowed desiccated disc Small shallow disc protrusion Modic 2 endplate changes	No changes in disc height No progression of Modic 2 endplate changes Disc protrusion reduced in size
08	L5/S1	Disc desiccation. Normal disc height. Shallow posterior disc protrusion. Hyperintense posterior peripheral zone	No changes in disc height No progression of endplate degenerative changes Stable disc protrusion and disc height Hyperintense posterior peripheral zone (annular fissure) has reduced in size
11	L5/S1	Disc desiccation with normal disc height Small annular fissure Broad based disc protrusion	No changes in disc height No progression of endplate degenerative changes Reduction in size of annular fissure
13	L3/4	Mild disc narrowing posteriorly Disc desiccation with very minor disc protrusion	No changes in disc height or disc protrusion No progression of endplate degenerative changes
14	L2/3	Disc desiccation. Very mild loss of disc height Small shallow disc protrusion. Inferior L2 endplate Schmorl's node with mild type 2 Modic endplate changes	No changes in disc height or disc protrusion No progression of endplate degenerative changes
16	L5/S1	Modic type 2 end plate changes Desiccated disc with moderate reduced height. Circumferential disc bulge	Disc bulge reduced in size Mild reduction in posterior disc space height No progression of endplate degenerative changes

pt: Patient.

Figure 8. MRI images showing two participants at (i) baseline and (ii) 12 months post procedure.

(A1 & 2) Represents participant 04 from Table 5 and shows no changes from baseline to follow-up. (A1) Participant 04, baseline. (A2) Participant 04, 12 months. (B1 & 2) Represents participant 07 from Table 5 and shows no changes in disc height, no progression of Modic 2 endplate changes and a reduction in disc protrusion size. (B1) Participant 05, baseline. (B2) Participant 05, 12 months.