BM-MSC Injection for Low Back Pain

Overseen By Katie Siebenaler

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Pain medications

Must not be taking: Immunosuppressants, Anti-rheumatics

Disqualifiers: Extreme obesity, Severe osteoporosis, Active malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to evaluate the safety and effect of bone marrow-derived stem cells for the treatment of low back pain.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those taking systemic immunosuppressants or anti-rheumatic medications within 3 months prior to enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment BM-MSC Injection for Low Back Pain?

Research shows that injecting bone marrow concentrate, which is rich in mesenchymal stem cells, can significantly reduce chronic back pain caused by degenerative disc disease. In a study, patients experienced a substantial reduction in pain scores over 12 months, indicating the potential effectiveness of this treatment. ^{1 2 3 4 5}

Is BM-MSC injection safe for humans?

The use of dimethyl sulfoxide (DMSO), a common component in BM-MSC injections, has been associated with some adverse effects, including minor toxicity and rare severe allergic reactions. In animal studies, DMSO has shown potential to cause brain cell damage, raising concerns about its safety, especially in children. However, removing DMSO from stem cell preparations has been shown to reduce these adverse effects. ^{6 7 8 9 10}

How does the BM-MSC injection treatment for low back pain differ from other treatments?

The BM-MSC injection treatment for low back pain is unique because it uses bone marrow-derived mesenchymal stem cells, which have the potential to regenerate damaged tissues and reduce pain, offering an alternative to surgery. This approach leverages the body's own cells to promote healing, which is different from traditional pain management methods that often rely on medication or invasive procedures. ^{1 11 12 13 14}

Research Team

Wenchun Qu, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with chronic low back pain lasting at least 6 months, diagnosed with facet joint arthropathy between L1-S1. Participants must not be pregnant, agree to use contraception, and have no recent back procedures or biological treatments. They should understand the study and consent to participate.

Inclusion Criteria

Persons of childbearing potential must have a negative serum pregnancy test and agree to use adequate contraception

My back pain was confirmed to be from facet joints by a successful nerve block test.

I have had low back pain for at least 6 months.

Exclusion Criteria

I take more than 50mg of pain medication daily.

You have a mental illness that might make it hard for you to finish the study or answer the questions in the study.

I have not had an epidural steroid injection in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intra-articular injections of allogeneic, culture-expanded BM-MSCs or DMSO

6 months

Single injection visit

Crossover

Participants initially receiving DMSO crossover to receive BM-MSC treatment

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

Treatment Details

Interventions

• BM-MSC injection
• DSMO Injection

Trial Overview The trial is testing the safety and effectiveness of bone marrow-derived stem cell (BM-MSC) injections compared to DMSO injections in treating lower back pain caused by facet joint arthropathy.

Participant Groups

Group I: Arm A Treatment Active Control 1 Intervention

Participants in Arm A will be scheduled for a single set of intra-articular injections of allogeneic, culture-expanded BM-MSCs at the dose 10 x106 in 1 ml per facet joint, for a total of 2 joints to be injected. BM-MSC injections will be performed using fluoroscopic guidance.

Group II: Arm B: DMSO Crossover Placebo Group 1 Intervention

Participants in Arm B will receive a DMSO injection. Following the BM-MSC or DMSO injection, each subject will be followed for study endpoints using a predetermined protocol. A final visit for evaluation and imaging will be conducted at the end of the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a study of 26 patients with chronic discogenic low back pain, intradiscal injections of bone marrow concentrate (BMC) were found to be safe, with no complications reported, and 92% of patients avoided surgery for at least 12 months.

The treatment resulted in significant and sustained pain relief, with average VAS scores decreasing from 80.1 mm to 22.9 mm over 24 months, and improvements in disability scores, indicating that BMC injections can be an effective non-surgical alternative for managing discogenic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Pettine, K., Suzuki, R., Sand, T., et al.[2022]

Bone marrow aspirate (BMA) contains a higher concentration of mesenchymal stem cells (MSCs) and more colony-forming units (CFUs) compared to bone marrow aspirate concentrate (BMAC), indicating that BMA may be more effective for cell-based therapies.

BMAC failed to concentrate MSCs in 6 out of 8 samples tested, highlighting significant variability in MSC quantity and potency between BMA and BMAC, which raises concerns about the reliability of BMAC for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. Brozovich, A., Sinicrope, BJ., Bauza, G., et al.[2022]

In a pilot study involving 26 patients with degenerative disc disease, autologous bone marrow concentrate (BMC) injections significantly reduced chronic back pain, with average Oswestry Disability Index (ODI) scores dropping from 56.5 to 25.0 and Visual Analog Scale (VAS) scores from 79.3 to 33.2 over 12 months (p ≤ .0001).

Patients receiving higher concentrations of mesenchymal stem cells (greater than 2,000 CFU-F/ml) experienced faster and greater pain reduction, highlighting the importance of cell concentration in the efficacy of BMC treatment for discogenic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Pettine, KA., Murphy, MB., Suzuki, RK., et al.[2022]

In a study of 55 patients with knee osteoarthritis, a single injection of autologous bone marrow aspirate concentrate (BMAC) led to significant improvements in patient-reported outcomes, including Tegner, VAS, and WOMAC scores.

The results suggest that BMAC is a beneficial and safe treatment option for knee osteoarthritis, as all measured outcomes showed statistically significant improvement from baseline to follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of bone marrow derived mesenchymal stem cells for the treatment of osteoarthritis: A retrospective long-term follow-up study. Mariani, C., Meneghetti, E., Zambon, D., et al.[2023]

Therapeutic levels of the antibiotics gentamicin and amikacin are highly toxic to equine bone marrow-derived mesenchymal stem cells (BM-MSCs), causing over 95% cell death within 45 minutes and 2 hours, respectively.

In contrast, hyaluronic acid and penicillin/streptomycin do not significantly harm BM-MSC viability, proliferation, or mediator secretion, suggesting that hyaluronic acid can be safely used with BM-MSCs without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells. Bohannon, LK., Owens, SD., Walker, NJ., et al.[2018]

In a review of 1,092 patients, 10 experienced severe neurological toxicity during the infusion of peripheral blood stem cells (PBSC) cryopreserved with DMSO, indicating a rare but serious risk associated with this treatment.

The neurological events included seizures and transient ischemic attacks, occurring in patients who received high concentrations of DMSO, suggesting that the infusion process and the use of citrate anticoagulant may contribute to these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe central nervous system toxicity associated with the infusion of cryopreserved PBSC components. Rowley, S., MacLeod, B., Heimfeld, S., et al.[2013]

The automated washing procedure using Sepax S-100 effectively maintained CD34+ cell counts and viability in stem cell transplants, showing no significant differences before and after washing.

Importantly, this method significantly reduced adverse reactions during infusion, with only one reported event compared to 14 adverse reactions in previous non-washed infusions, highlighting its safety benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion. Sánchez-Salinas, A., Cabañas-Perianes, V., Blanquer, M., et al.[2013]

Adipose tissue MSCs (Ad-MSCs) showed significantly higher viability after cryopreservation in the serum- and xeno-free STEM-CELLBANKER™ (CB) compared to 10% dimethyl sulfoxide (DMSO), with viability rates of 90.4% versus 79.9%.

Both Ad-MSCs and bone marrow MSCs (BM-MSCs) maintained their differentiation potential after cryopreservation in both cryoprotectants, but the characteristics of Ad-MSCs were better preserved in CB, suggesting that CB may be a superior option for MSC cryopreservation in cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defined serum- and xeno-free cryopreservation of mesenchymal stem cells. Al-Saqi, SH., Saliem, M., Quezada, HC., et al.[2018]

DMSO, a common solvent used in bone marrow and organ transplantation, caused widespread apoptosis (cell death) in the developing brains of mice at all tested ages, with the most significant damage observed at postnatal day 7.

The study raises concerns about the safety of DMSO in children undergoing bone marrow transplantation, as they are often exposed to doses higher than the lowest effective dose (0.3 ml/kg) that already produced significant neuronal damage in mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Hanslick, JL., Lau, K., Noguchi, KK., et al.[2023]

Transplantation of DMSO-depleted allogeneic peripheral blood stem cells (PBSCs) in 21 patients showed a low incidence of infusion-related adverse effects, with only three patients experiencing complications.

The median recovery times for neutrophils and platelets were 13.0 and 14.0 days, respectively, indicating that removing DMSO from PBSCs is both safe and effective for enhancing patient recovery post-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cryoprotectant-depleted allogeneic peripheral blood stem cells for transplantation. Hirata, Y., Kishino, K., Onozaki, F., et al.[2011]

Infusing bone marrow stromal cells (BMSCs) into the cerebrospinal fluid (CSF) significantly improved locomotor function in rats with subacute and chronic spinal cord injuries, with BBB scores increasing from 1.0-3.5 to 9.0-10.9 after treatment, compared to only 0.5-4.0 to 3.0-5.1 in control groups.

BMSCs appear to promote axonal regeneration and neuron survival, suggesting they may act as neurotrophic sources, although very few BMSCs survived in the spinal cord lesion after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats. Nakano, N., Nakai, Y., Seo, TB., et al.[2021]

In a study of 26 patients with degenerative disc disease, intradiscal injections of bone marrow concentrate (BMC) showed significant improvements in pain and disability scores after 36 months, with only 6 patients requiring surgery.

The treatment was found to be safe, with no adverse events reported, and MRI results indicated that 40% of patients improved in disc degeneration without any worsening, suggesting BMC therapy is a feasible alternative to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Pettine, KA., Suzuki, RK., Sand, TT., et al.[2022]

Intradiscal injections of concentrated bone marrow aspirate (cBMA) showed potential effectiveness in reducing low back pain (LBP), with at least 50% improvement observed in a significant proportion of patients over a year-long follow-up.

Patients with higher baseline pain levels (NRS > 5) experienced greater improvements compared to those with lower baseline pain, suggesting that cBMA may be particularly beneficial for individuals with more severe pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis. Wolff, M., Shillington, JM., Rathbone, C., et al.[2020]

Baculo-BMP-7-modified bone marrow-derived mesenchymal stem cells (BMDMSCs) significantly improved disc height in degenerative discs in rats compared to standard BMDMSCs, indicating enhanced efficacy in slowing degeneration.

Early treatment with Baculo-BMP-7-BMDMSCs (at zero weeks) resulted in better outcomes in disc height and lower histology scores compared to treatments starting at two or four weeks, suggesting that timing of intervention is crucial for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell Therapy Using Bone Marrow-Derived Stem Cell Overexpressing BMP-7 for Degenerative Discs in a Rat Tail Disc Model. Liao, JC.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

High Variability of Mesenchymal Stem Cells Obtained via Bone Marrow Aspirate Concentrate Compared With Traditional Bone Marrow Aspiration Technique. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Use of bone marrow derived mesenchymal stem cells for the treatment of osteoarthritis: A retrospective long-term follow-up study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Severe central nervous system toxicity associated with the infusion of cryopreserved PBSC components. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

An automatic wash method for dimethyl sulfoxide removal in autologous hematopoietic stem cell transplantation decreases the adverse effects related to infusion. [2013]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Defined serum- and xeno-free cryopreservation of mesenchymal stem cells. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Use of cryoprotectant-depleted allogeneic peripheral blood stem cells for transplantation. [2011]

11. United States pubmed.ncbi.nlm.nih.gov

Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis. [2020]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Cell Therapy Using Bone Marrow-Derived Stem Cell Overexpressing BMP-7 for Degenerative Discs in a Rat Tail Disc Model. [2018]