The ANOVA Back Pain Stem Cell Treatment Programme Germany

Low back pain is the leading cause of years lived with disability worldwide.^[1] A standard MRI shows disc bulges and wear, but these are also common in people without any pain. We therefore look for the structure that is actually inflamed: a vertebral body, a facet joint, a spinal ligament or a compressed nerve root. The programme is offered alongside — never instead of — exercise, physiotherapy and treatment by your doctors.

Back pain is pain in the neck, upper back or lower back; when it lasts longer than three months, it is called chronic. About 619 million people worldwide had low back pain in 2020, and almost everyone has it at some point in life.^[1],[2] In most people no single cause can be found. In some, the pain comes from a worn intervertebral disc (degenerative disc disease) or from the small joints of the spine (facet joints). Other sources are inflamed vertebral bodies or a nerve root compressed by a herniated disc.^[2]

Back and neck pain is not the same as pain in the knee, hip or shoulder. Those joints are covered on our joints and sport injuries page, and osteoarthritis of the limbs on our osteoarthritis page. Osteoarthritis of the small joints of the spine (facet joints) belongs here.

Typical symptoms are:

• Pain in the lower back, neck or between the shoulder blades, often worse on bending, lifting or sitting
• Pain radiating into a leg (sciatica) or an arm, sometimes with numbness, tingling or weakness
• Stiffness in the morning or after long periods in one position
• Pain that comes in flare-ups and calmer phases

Doctors distinguish the lumbar spine (lower back), the thoracic spine and the cervical spine (neck). Common diagnoses are herniated disc, degenerative disc disease (DDD), spinal stenosis and facet joint arthritis; inflamed vertebral endplates show on MRI as Modic changes. To date no cure is known for degenerative disc disease. More details can be found below in our scientific section on back pain.

ANOVA offers autologous bone marrow concentrate (BMC) for back and neck pain caused by inflammation. The programme has two components: a precision MRI to find the source of pain, and BMC injected precisely at that site. Each component is selected individually; the programme is not a fixed package.

Pain often arises where a structure of the spine is inflamed. BMC contains stem cells and growth factors that are thought to communicate with the immune cells involved and to dampen this inflammation. It is injected into the inflamed vertebral body, facet joint, spinal ligament or disc, with the aim of reducing the pain and slowing further wear. Where a disc presses on a nerve purely mechanically, BMC is not the right treatment.

ANOVA IRM has not yet tested BMC for back pain in a clinical study. The current state of research is described in the clinical and scientific section below.

Our MRI of the spine is carried out with an intravenous contrast agent, which makes active inflammation visible. For the neck we add angled (oblique) views, because the nerve roots leave the cervical spine at an angle that routine images do not capture. From this we see which structure is inflamed and where BMC should be placed.

BMC is made from your own bone marrow and contains haematopoietic and mesenchymal stem cells in their natural composition, together with growth factors. It is collected from the pelvic bone (iliac crest) under brief sedation, concentrated, tested and injected under CT guidance on the same day, during a two-day visit. BMC is our main option when back pain arises from one or a few segments of the spine. The current state of research is set out in the clinical and scientific section below.

After a diagnostic work-up we treat the following conditions of the lumbar, thoracic and cervical spine with BMC, where MRI shows inflammation at the source of pain:

• Degenerative disc disease and degenerative changes of the discs
• Inflamed vertebral bodies with Modic changes (active osteochondrosis)
• Facet joint syndrome and facet joint arthritis (facet arthropathy)
• Inflammation of the spinal ligaments (inter- and paraspinal ligaments)
• Chronic pain and inflammation of the spine after strains or minor injuries of vertebrae and ligaments

A herniated disc (disc prolapse) that compresses a nerve purely mechanically is not treated with BMC; we discuss other options with you. Spinal cord injuries are covered on our spinal cord injury page.

We look for the cause of your pain. Dr. Stehling, founder of ANOVA IRM, is a radiologist and physicist. We work with the Prof. Dr. Stehling Institut für Bildgebende Diagnostik GmbH, which, like ANOVA IRM, belongs to Dr. Stehling and is located in the same building. Disc bulges and wear are common on MRI even in people without back pain, so a standard scan alone often does not explain the pain.^[5] Contrast-enhanced MRI shows active inflammation, which points to the actual source of pain.

Which tests are used to diagnose back pain?

Diagnosis starts with your history and a physical examination, including the nerves of the legs or arms. MRI shows discs, vertebrae, facet joints, ligaments and nerve roots; with contrast it also shows inflammation. In the neck, angled (oblique) MRI views show the openings through which the nerve roots leave the spine more reliably than routine images.^[7] X-ray and CT show the bone; blood tests prepare the treatment.

What do we review before back pain treatment at ANOVA IRM?

Before any treatment decision we review which structure causes your pain, whether it is inflamed and whether a nerve is compressed mechanically. We also check whether you are fit for the brief sedation needed for the bone marrow collection.

With BMC:

• Standard: no MRI required if recent, suitable images are available.
• Optional, often decisive: MRI with intravenous contrast and, for the neck, angled views.
• CT-guided application: always in the lumbar spine.

Your own doctors at home can carry out these examinations; please send us the results. Because few radiology departments routinely use contrast and angled views of the spine, we often recommend having them done in-house, where an MRI is often possible on the day of your appointment. If you would like existing findings assessed independently, we offer a second opinion. The full diagnostic pathway is described on our diagnostics page.

Our approach starts with diagnostics. Imaging is led by radiologists, and we have developed our own MRI protocols for disc and spine conditions. BMC is placed under imaging guidance into the inflamed structure: always under CT in the lower back, elsewhere under CT or X-ray fluoroscopy. An anaesthesiologist looks after you during the bone marrow collection, with the aim of keeping it as pain-free as possible. ANOVA IRM has manufactured BMC in its own facility in Offenbach since 2018; why no marketing authorisation is needed is explained on our regulatory status page. We advise international patients in English.

First our patient care team tells you which information we need, such as MRI, CT or X-ray images and reports from your orthopaedic surgeon, and how to send large image files. We review your findings and images, also if you only want a second opinion on your conservative treatment. A counselling appointment with one of our physicians follows, by phone or video if you live outside Germany; on-site appointments are possible too. Our patient care team does not charge for its services. Before you decide, you receive an individual written cost estimate.

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BMC treatment for back pain at ANOVA IRM costs approximately €8,000–€9,000 and requires one two-day outpatient visit to Offenbach, Germany. It is available to adults with chronic back or neck pain in whom precision MRI shows inflammation at the source of pain.

1. 01
   Remote assessment

   Review of your history, previous treatment and images by email, phone or video; two weeks to a few months, depending on available appointments.

2. 02
   Screening at home

   Blood test and recent images before you travel, to avoid an unnecessary journey.

3. 03
   Day 1 in Offenbach

   Consultation and consent, blood tests and, where needed, MRI with contrast; planning of the injection site.

4. 04
   Day 2 in Offenbach

   Bone marrow collection under brief sedation; BMC is concentrated, tested and injected under CT guidance the same day.

5. 05
   Follow-up

   Exercise and physiotherapy at home; review of your progress by phone or video; a repeat treatment is possible after assessment.

BMC may be considered for adults with chronic back or neck pain that persists despite exercise, physiotherapy and medication, after a full diagnostic work-up. Most suitable are patients in whom MRI shows inflammation in one or a few segments, such as a vertebral body, facet joint, ligament or disc. Requirements are fitness for the brief sedation used for the bone marrow collection and a visit to Offenbach. Your doctor weighs the possible benefit against the risks for you and recommends treatment only where the benefit is likely to outweigh them.

What are the contraindications for back pain treatment?

Our treatments are experimental. We treat only people for whom, after medical assessment, we consider the benefit-risk balance to support treatment.

Applies to all ANOVA treatments:

• Active cancer within the last two years
• Under the age of legal majority
• Pregnancy or breastfeeding
• Active infectious disease (hepatitis A, B, C, HIV, syphilis or other)

Specific to back pain:

• Rapidly increasing weakness or loss of control in the legs — this needs urgent surgical assessment
• Infection of the spine or of the skin at the injection site
• Unable to breathe unaided, difficulty breathing in the supine position or severe difficulty swallowing (dysphagia), because of the sedation
• Psychiatric disorder that would prevent informed consent or cooperation

A blood clotting disorder or blood-thinning medication is not in itself a contraindication, but please tell us about it before your visit.

Treatment for back pain follows fixed phases. We begin with your medical history, your previous treatments and an initial consultation with an indication statement on whether BMC may help you. Preliminary examinations, precision diagnostics, a discussion of all treatment options and a written plan with cost estimate follow. Finally, bone marrow is collected, BMC is prepared and tested, and it is injected at the source of pain.

What screening is needed before you travel for back pain treatment?

A short screening in your home country helps you avoid a journey that would not lead to treatment. It usually consists of a blood test for infections and other reasons against treatment, plus your recent spine images and doctors’ letters.

What happens at your visit to Offenbach for back pain?

You spend two consecutive days in Offenbach as an outpatient. On day one, your doctor explains the treatment, obtains your consent and takes blood; an MRI with contrast can be added. On day two, bone marrow is taken from the pelvic bone under brief sedation, and BMC is injected under CT guidance a few hours later.

How is your BMC produced and quality-controlled?

BMC is prepared on the day of collection in our own facility in Offenbach, under a manufacturing authorisation (Section 13 AMG) and good manufacturing practice (GMP). The bone marrow is concentrated but not multiplied in the laboratory; key quality tests are completed before the injection, further tests follow afterwards.

How is BMC applied in back pain?

BMC for back pain is given during one visit of two days, as with all BMC treatments. Degenerative disc disease and facet joint disease are chronic; BMC is intended to modify their course (disease-modifying), not to cure them. The treatment may therefore need to be repeated. The schedule is set individually for each patient, for example:

• Standard route for back pain: local injection into the disc (intradiscal), the facet joint, the inflamed vertebral body or the affected ligament, depending on the source of pain
• Several segments can be treated during the same visit; depending on the area to be treated, a double BMC may be needed
• CT guidance: always in the lumbar spine
• BMC is given only locally, never into a vein
• A repeat after assessment requires a new bone marrow collection

BMC treatment for back pain costs approximately €8,000 to €9,000 and is billed according to the German Medical Fee Schedule (GOÄ). As CT always guides the injection in the lumbar spine, the cost there is closer to €9,000. An MRI with contrast beforehand, the number of treated segments, a double BMC where the area to be treated requires it, and your wishes regarding sedation also affect the total. Treatment is generally self-funded. Before any decision you receive an individual written estimate. Our blog post on treatment cost explains what drives the cost of stem cell treatment in general. Travel and accommodation are not included. All prices are subject to change.

How does the cost of back pain treatment vary with the application route?

All treatments at ANOVA IRM are billed according to the German Medical Fee Schedule (Gebührenordnung für Ärzte, GOÄ). For back pain, BMC is always injected locally; the cost depends mainly on CT guidance, on the number of segments, on whether a double BMC is needed and on any MRI beforehand. Your written cost estimate shows the exact amount.

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An intervertebral disc consists of a gel-like core (nucleus pulposus) surrounded by a fibrous ring (annulus fibrosus). In a healthy disc, the core binds water and acts as a shock absorber between two vertebrae. With age and load, the core loses water, the disc loses height and the openings through which the nerve roots leave the spine (neuroforamina) narrow. The ring can tear, and parts of the core can bulge or herniate and press on a nerve root.^[2] The adjacent vertebral endplates can become inflamed, and the facet joints wear down because they carry more load.

Unlike osteoarthritis of the knee or hip, degeneration of the spine affects a chain of structures at once: disc, vertebral endplates, facet joints, ligaments and nerve roots. In rheumatoid arthritis, the spine is rarely the starting point. Injuries of the joints of the limbs are covered on our joints page.

What causes back pain, and what are the risk factors?

Most back pain cannot be traced to a single structure. In about four in ten people with chronic low back pain, a damaged disc (internal disc disruption) is the source.^[3] Other sources are the facet joints, inflamed vertebral endplates, the sacroiliac joints and the spinal ligaments. The main risk factors are:^[2]

• Older age and wear of the discs
• Physically heavy work, lifting and long periods of sitting, for example at a computer with a poor posture
• Lack of exercise and excess weight
• Smoking
• Earlier injuries of the spine, for example from sport or accidents
• Stress, low mood and fear of movement, which make pain more likely to become chronic

What drives the progression of back pain and disc degeneration?

The cause and what drives it forward are two separate questions. Once a disc is damaged, the cells in its core produce enzymes and inflammatory messengers that break down the matrix further. Tissue from a torn disc can trigger inflammation around the nerve root, and overloaded facet joints and endplates become inflamed in turn. Inactivity and fear of movement can keep the pain going.^[2] Our programme is aimed at this inflammation, not at the original cause.

According to international guidelines, the core treatment of back pain consists of information, staying active, exercise therapy and physiotherapy; psychological approaches help with chronic pain.^[8] The standard of care also includes:

• Pain medication for a limited time, mainly non-steroidal anti-inflammatory drugs; details on medication are on our osteoarthritis page
• Injections near the nerve root (epidural or periradicular) or into the facet joints, with cortisone and a local anaesthetic
• A diagnostic test injection: a local anaesthetic into the suspected source of pain; if the pain improves, this helps to confirm the source
• Radiofrequency denervation of the facet joints and ablation of the basivertebral nerve for selected patients
• Intradiscal treatment of a herniated disc, for example with gelified ethanol (an alcohol gel that shrinks the herniated tissue)
• Surgery: removal of disc tissue (microdiscectomy), decompression of a nerve root or the spinal canal, spinal fusion or an artificial disc

Glucosamine injections and heating of the disc (intradiscal electrothermal therapy, IDET) are being investigated; hyaluronic acid, used mainly in joints, is described on our osteoarthritis page.

What do interventional procedures for back pain achieve?

Ablation of the basivertebral nerve (the nerve inside the vertebral body that carries pain from the endplates) treats pain from inflamed vertebral endplates (Modic changes) with heat. In a sham-controlled external study, function improved more than with a sham procedure after three months in the patients treated according to protocol, and pooled external data show lasting improvement after five years.^[9],[10] In an external study, radiofrequency denervation of the facet joints (heat to switch off the small nerves of these joints) helped many carefully selected patients for more than a year.^[11] In three external randomised studies, however, a clinically important benefit in addition to an exercise programme could not yet be demonstrated.^[12]

Injection of gelified ethanol into a herniated disc improved symptoms in most patients in external case series without a control group.^[13],[14] In the neck, nerve roots are often compressed by worn uncovertebral joints (small joints at the sides of the cervical vertebrae) rather than by a disc. An operation from behind can preserve the natural disc where it is suitable.

How do common back pain treatments compare in effect, risks and side effects?

What can you do yourself with back pain: exercise, posture and sport?

Staying active is the most important thing you can do yourself. Before chiropractic, osteopathic or manual treatment of the spine, a fracture or a herniated disc should be ruled out by MRI. A physiotherapist can show you stabilising exercises for the back and neck muscles that, done regularly, can improve movement and reduce pain. Check whether your legs are the same length and whether a pelvic misalignment loads your spine on one side.

In many cases, moderate sport helps. With neck problems, cycling on an upright bike is better than a racing bike; have the saddle height adjusted first. Swimming is gentle on the spine, especially front crawl, backstroke or breaststroke with a float. Walking and Nordic walking are also suitable; your physiotherapist advises which movements to avoid. Losing excess weight and stopping smoking relieve the spine. We are glad to advise you on supplements and infusion therapies alongside your treatment.

When is spinal surgery or an artificial disc needed for back pain?

Surgery is needed urgently when nerves are severely compressed, with paralysis or loss of bladder or bowel control. Otherwise it is an option when pain and limitation persist despite conservative treatment and the source is clearly identified. For many operations on the lower back, the evidence of benefit over conservative treatment is limited.^[15] An artificial disc (total disc replacement) preserves movement of the segment, while fusion stiffens it; both require weeks to months of rehabilitation. The risks of lumbar disc replacement are summarised by Johns Hopkins Medicine.

Stem cell therapy is therefore an option some patients consider before spinal surgery, with the aim of postponing it. Whether BMC can postpone or avoid an operation has not been investigated in controlled studies.

How is back pain diagnosed, and what do we not do ourselves?

Back pain is diagnosed from the history, a physical and neurological examination and, where needed, imaging. Typical X-ray findings of degenerative disc disease (DDD) are a narrowed disc space, displacement of vertebrae and bony spurs (osteophytes). MRI grades disc degeneration on the Pfirrmann scale, from grade I, a healthy bright disc of normal height, to grade V, a collapsed dark disc.^[6] Disc bulges are found in about 30% of 20-year-olds and 84% of 80-year-olds without back pain, so findings must match the symptoms.^[5] Physiotherapy, interventional procedures and operations stay with your treating doctors; we carry out MRI and CT ourselves at the Institut für Bildgebende Diagnostik in the same building.

Bone marrow concentrate (BMC)

ANOVA IRM has not yet tested BMC for back pain in a clinical study. In a small external study without a control group, 26 patients with degenerative disc disease received BMC into the disc. After three years, 6 had needed surgery; in the other 20, the Oswestry Disability Index (ODI, a questionnaire on limitations in everyday life) fell from 57 to 18 and pain fell markedly.^[16],[17] MRI after one year showed a better Pfirrmann grade in 40%, and no patient worsened. A retrospective external analysis also reported less pain and better function after BMC.^[18]

In an older small external study with haematopoietic stem cells from bone marrow injected into the disc, a reduction of pain after one year could not yet be demonstrated.^[19] Studies of BMC injected into vertebral bodies, facet joints or spinal ligaments are, to our knowledge, not available. There is no phase 3 study of BMC in back pain.

What is the efficacy hypothesis behind BMC in back pain?

In a degenerated disc, few cells remain and the environment is dominated by breakdown and inflammation. Stem cells and their messengers (the secretome) are thought to communicate with the remaining disc cells and the immune cells. They are thought to dampen inflammation in the disc, the endplates and the facet joints and so reduce pain. Whether this can also slow the breakdown of the disc is being investigated; BMC is not intended to rebuild a collapsed disc.

Mesenchymal stem cells and secretome — analogous evidence

Studies with cultured mesenchymal stem cells, a different product from BMC, point in the same direction. In a small external pilot study, cells from the patients’ own bone marrow injected into the disc reduced pain and disability, and the disc held more water after one year.^[20] In a small external randomised study with donor cells, pain and disability improved more than in the control group, mainly in a subgroup of responders.^[21] In external laboratory studies, stem cells and disc core cells exchanged membrane components and extracellular vesicles, which are part of the secretome.^[24],[25] A review summarises these mechanisms.^[26]

In an external phase 3 study, 404 patients received cultured donor mesenchymal precursor cells, again a different product from BMC, into the disc. Its predefined combined goal for pain, function and no further intervention could not yet be demonstrated.^[22] A second external phase 3 study with this product is under way; its main results are expected from mid-2027.^[23]

Senescent cells in disc degeneration

Ageing (senescent) cells accumulate in degenerating discs and release inflammatory messengers. In an external laboratory and animal study in mice, removing such cells reduced age-related disc degeneration.^[27] Whether this applies to people with back pain is not known. Senolytic therapy is not part of the back pain programme; it is described on our senolytic therapy page.

Talk to us about current changes or additions to the back pain programme. For a number of conditions, ANOVA IRM also offers infusion therapies alongside the treatment described here.

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We have not yet evaluated our own data on back pain. This section therefore summarises published external evidence, not our own patient outcomes. Some patients describe their experience on our testimonials page; these are individual accounts, not evidence that a treatment works.

How do we assess the course after back pain treatment?

After treatment, we ask about and assess the following:

• Pain, measured on a visual analogue scale (VAS)
• Disability in everyday life, measured with the Oswestry Disability Index (ODI)
• Radiating pain, numbness and strength in the legs or arms
• Use of pain medication and further injections
• MRI of the treated segment, where useful, including the Pfirrmann grade

What the published back pain evidence does not yet tell us

• Most studies of BMC in the disc are small, and none has a placebo control.
• The bone marrow products studied were prepared and dosed differently from BMC at ANOVA IRM.
• Long-term safety data are limited, including whether long-term side effects known from cortisone are avoided.
• In Germany and the EU, no stem cell-based treatment is approved as a standard treatment for back pain.

For back pain, ANOVA IRM uses BMC, an advanced therapy medicinal product. It is manufactured under a procurement authorisation (Section 20b AMG) and a manufacturing authorisation (Section 13 AMG) of the Hessian State Office for Health and Care (HLfGP), which inspects the facility regularly. The injection into the spine is given as an individual treatment attempt (individueller Heilversuch), after full disclosure and with your informed consent. As BMC is used only for our own patients, it requires no authorisation under Section 4b, no marketing authorisation under Section 21 and no approval under Section 21a AMG. More on our regulatory status page.

Questions people usually ask next. Each is answered in full on its own page.

• Who are we?
• Is ANOVA legal?
• Is stem cell therapy safe?
• What is BMC (Bone Marrow Concentrate)?
• What is the stem cell secretome?
• What are stem cells?
• What should I ask when looking for a stem cell treatment?
• Which stem cell therapies does ANOVA offer?
• Which conditions do we treat?
• Joint and back pain — overview
• Joints and sport injuries
• Osteoarthritis
• Spinal cord injury

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ANOVA IRM shares its premises in Offenbach with two further institutions owned by Dr. Stehling: the Institut für Bildgebende Diagnostik (IBDO), providing MRI and CT imaging, and the VITUS PRIVATKLINIK Prof. Dr. Stehling GmbH. Because imaging is carried out in the same building, contrast-enhanced and angled MRI of the spine and CT-guided injections can be performed in-house. See diagnostics at ANOVA IRM.

General literature on joint and back pain is maintained on the pillar page, and on bone marrow on the BMC page.

Back pain and disc degeneration — frequency, causes and course

• [1] GBD 2021 Low Back Pain Collaborators. Global, regional, and national burden of low back pain, 1990–2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5(6):e316–e329. doi:10.1016/S2665-9913(23)00098-X. PMID: 37273833.
• [2] Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391(10137):2356–2367. doi:10.1016/S0140-6736(18)30480-X. PMID: 29573870.
• [3] Schwarzer AC, Aprill CN, Derby R, et al. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine (Phila Pa 1976). 1995;20(17):1878–1883. doi:10.1097/00007632-199509000-00007. PMID: 8560335.
• [4] Chiu CC, Chuang TY, Chang KH, et al. The probability of spontaneous regression of lumbar herniated disc: a systematic review. Clin Rehabil. 2015;29(2):184–195. doi:10.1177/0269215514540919. PMID: 25009200.

Diagnostics and imaging of the spine

• [5] Brinjikji W, Luetmer PH, Comstock B, et al. Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. AJNR Am J Neuroradiol. 2015;36(4):811–816. doi:10.3174/ajnr.A4173. PMID: 25430861.
• [6] Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976). 2001;26(17):1873–1878. doi:10.1097/00007632-200109010-00011. PMID: 11568697.
• [7] Shim JH, Park CK, Lee JH, et al. A comparison of angled sagittal MRI and conventional MRI in the diagnosis of herniated disc and stenosis in the cervical foramen. Eur Spine J. 2009;18(8):1109–1116. doi:10.1007/s00586-009-0932-x. PMID: 19294432.

Standard of care: guidelines, interventional procedures and surgery

• [8] Foster NE, Anema JR, Cherkin D, et al. Prevention and treatment of low back pain: evidence, challenges, and promising directions. Lancet. 2018;391(10137):2368–2383. doi:10.1016/S0140-6736(18)30489-6. PMID: 29573872.
• [9] Fischgrund JS, Rhyne A, Franke J, et al. Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study. Eur Spine J. 2018;27(5):1146–1156. doi:10.1007/s00586-018-5496-1. PMID: 29423885.
• [10] Khalil JG, Truumees E, Macadaeg K, et al. Intraosseous basivertebral nerve ablation: a 5-year pooled analysis from three prospective clinical trials. Interv Pain Med. 2024;3(4):100529. doi:10.1016/j.inpm.2024.100529. PMID: 39758714.
• [11] Conger A, Burnham T, Salazar F, et al. The effectiveness of radiofrequency ablation of medial branch nerves for chronic lumbar facet joint syndrome in patients selected by guideline-concordant dual comparative medial branch blocks. Pain Med. 2020;21(5):902–909. doi:10.1093/pm/pnz248. PMID: 31609391.
• [12] Juch JNS, Maas ET, Ostelo RWJG, et al. Effect of radiofrequency denervation on pain intensity among patients with chronic low back pain: the Mint randomized clinical trials. JAMA. 2017;318(1):68–81. doi:10.1001/jama.2017.7918. PMID: 28672319.
• [13] Bellini M, Romano DG, Leonini S, et al. Percutaneous injection of radiopaque gelified ethanol for the treatment of lumbar and cervical intervertebral disk herniations: experience and clinical outcome in 80 patients. AJNR Am J Neuroradiol. 2015;36(3):600–605. doi:10.3174/ajnr.A4166. PMID: 25395657.
• [14] Latka K, Kozlowska K, Waligora M, et al. Efficacy of DiscoGel in treatment of degenerative disc disease: a prospective 1-year observation of 67 patients. Brain Sci. 2021;11(11):1434. doi:10.3390/brainsci11111434. PMID: 34827432.
• [15] Jacobs WC, Rubinstein SM, Willems PC, et al. The evidence on surgical interventions for low back disorders, an overview of systematic reviews. Eur Spine J. 2013;22(9):1936–1949. doi:10.1007/s00586-013-2823-4. PMID: 23681497.

Bone marrow concentrate (BMC) in degenerative disc disease

• [16] Pettine KA, Murphy MB, Suzuki RK, et al. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015;33(1):146–156. doi:10.1002/stem.1845. PMID: 25187512.
• [17] Pettine KA, Suzuki RK, Sand TT, et al. Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop. 2017;41(10):2097–2103. doi:10.1007/s00264-017-3560-9. PMID: 28748380.
• [18] Wolff M, Shillington JM, Rathbone C, et al. Injections of concentrated bone marrow aspirate as treatment for discogenic pain: a retrospective analysis. BMC Musculoskelet Disord. 2020;21(1):135. doi:10.1186/s12891-020-3126-7. PMID: 32111220.
• [19] Haufe SM, Mork AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev. 2006;15(1):136–137. doi:10.1089/scd.2006.15.136. PMID: 16522171.

Mesenchymal stem cells and secretome — analogous evidence, not BMC itself

• [20] Orozco L, Soler R, Morera C, et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011;92(7):822–828. doi:10.1097/TP.0b013e3182298a15. PMID: 21792091.
• [21] Noriega DC, Ardura F, Hernández-Ramajo R, et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation. 2017;101(8):1945–1951. doi:10.1097/TP.0000000000001484. PMID: 27661661.
• [22] Mesoblast, Ltd. A prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a single injection of rexlemestrocel-L alone or combined with hyaluronic acid (HA) in subjects with chronic low back pain (MSB-DR003). Phase 3, 404 participants, completed 2021, results posted. ClinicalTrials.gov NCT02412735 (manufacturer-sponsored; registry results, no peer-reviewed full publication).
• [23] Mesoblast, Ltd. A prospective, multicenter, randomized, double-blind, controlled study to evaluate the efficacy and safety of a single injection of rexlemestrocel-L combined with HA in subjects with moderate to severe chronic low back pain (MSB-DR004). Phase 3, ongoing; primary completion estimated July 2027. ClinicalTrials.gov NCT06325566 (manufacturer-sponsored).
• [24] Strassburg S, Richardson SM, Freemont AJ, et al. Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med. 2010;5(5):701–711. doi:10.2217/rme.10.59. PMID: 20868326.
• [25] Strassburg S, Hodson NW, Hill PI, et al. Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells. PLoS One. 2012;7(3):e33739. doi:10.1371/journal.pone.0033739. PMID: 22438989.
• [26] Drazin D, Rosner J, Avalos P, et al. Stem cell therapy for degenerative disc disease. Adv Orthop. 2012;2012:961052. doi:10.1155/2012/961052. PMID: 22593830.

Senescent cells in disc degeneration

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