Bone Marrow Concentrate (BMC) Germany

BMC is made from your own bone marrow and is applied on the day of collection. The cells are concentrated but not multiplied in the laboratory, and no donor material is used. ANOVA IRM manufactures BMC in Offenbach, Germany, under a procurement authorisation (Section 20b AMG) and a manufacturing authorisation (Section 13 AMG). How ANOVA IRM is regulated is explained on our regulatory status page. BMC is experimental and is given as an individual treatment attempt (individueller Heilversuch) after a personal medical assessment. Since 2019, 153 people have been treated with BMC at ANOVA IRM (as of October 2026). ANOVA IRM also offers the cell-free MSC secretome (MSEC); how the two products differ is explained on our page About Stem Cell Therapy.

In this section:

• What is BMC - What is Bone Marrow Concentrate?
• Why is BMC a Stem Cell Concentrate?
• Why Do We Get Stem Cells From the Bone Marrow?
• What is a BMC Therapy?
• BMC or MSEC? Pros and Cons
• Frequently Asked Questions — Bone Marrow Concentrate
• Vocabulary and Definitions

Bone Marrow Concentrate (BMC) is a fluid taken from the patient’s iliac crest. It consists of blood and bone marrow stem cells, which are flushed out of the pelvic bone together when BMC is taken out using a syringe. The composition thus corresponds to the natural composition of a mixture of blood and bone marrow.

This mixture contains, among others, hematopoietic stem cells and so-called mesenchymal stem cells (named after their belonging to the middle layer of the body, the mesenchyme). In addition, the white blood cells found in the blood, such as myeloid cells (neutrophils, basophils, eosinophils, monocytes) and platelets, as well as lymphoid white blood cells (T cells and B cells).

BMC contains two kinds of stem cells: blood-forming (haematopoietic) stem and progenitor cells, about 1 % of the nucleated cells, and mesenchymal stem cells, a much smaller share of well under 0.1 % ^[3],[6],[12]. Most cells in BMC are other blood and immune cells. External laboratory research suggests that the effect does not depend on one cell type alone, but on the whole mixture of cells and the growth factors they release ^[13],[24]. In the scientific literature, BMC is also called bone marrow aspirate concentrate (BMAC). How bone marrow stem cells relate to other stem cell types is explained on our page About Stem Cell Therapy.

Conditions in Which BMC Is Currently Used at ANOVA

The following conditions are areas in which BMC is applied at ANOVA and in which the treatment is being investigated in early clinical research. A benefit for the individual patient cannot be predicted or promised. We determine for each patient whether in this specific case stem cells are an advisable treatment strategy. There are also several contraindications such as being under 18 years of age, pregnant, having breathing difficulties, acute cancer etc. Please inquire with our patient care managers whether BMC could be an option for you.

• Osteoarthritis
• Knee - Meniscus Tears (medial and lateral), Chondromalacia Patella, Tendon Injuries (Patellar Tendinitis, Quad Tendon), Ligament sprains or tears (MCL, LCL, ACL)
• Hip - Hip Labrum Tears, SI Joint Dysfunction, Piriformis Syndrome, Greater Trochanteric Bursitis, Iliotibial Band (ITB) Syndrome
• Shoulder - Rotator Cuff Tendinitis, Tendinopathy, or Partial Tears, Labrum Tear, Bicipital Tendinitis
• Elbow - Lateral Epicondylitis (Tennis Elbow), Medial Epicondylitis (Golfer’s Elbow)
• Hand or Wrist Pain - De Quervain’s Tenosynovitis
• Ankle & Foot Pain - Achilles Tendinitis or Partial Tears, Plantar Fasciitis, Ankle sprains or ligament injury
• Spine - Facet Joint Arthropathy. Sacroiliac (SI) Joint Dysfunction
• Erectile dysfunction
• Rheumatoid arthritis — individual affected joints

Knee, hip, shoulder, elbow, hand and ankle injuries are described on our page on joint injuries. If you have questions about whether BMC can be considered in your situation, please contact our physicians.

BMC is named a stem cell concentrate because after the minimally invasive collection, part of the blood serum is removed so that the cells are contained in a smaller volume.

Blood serum and erythrocytes (red blood cells) are partially excluded from BMC, thereby increasing the stem cells concentration per mL. At ANOVA IRM, BMC is concentrated about sixfold compared with the bone marrow aspirate.

This is especially important when the stem cells are to be injected into small joints because the joint space is very small. However, no further manipulation takes place on the BMCs.

The cell composition corresponds to the natural composition of bone marrow, in concentrated form.

The stem cells are not further manipulated, not cultivated or multiplied. They are re-applied directly after the quality control tests that are carried out before application (see Quality Control and Release of BMC).

The whole procedure of donation, concentration, quality control and re-application takes place on the same day.

Bone marrow can be found in the central region of your bones and is a soft spongy tissue which produces your red bloods cells, white blood cells and blood plasma components. Stem cells (hematopoietic as well as mesenchymal stem cells) can be found in this tissue, as they play a key role in the production of these cell components.

In contrast to other body regions that contain stem cells, the bone marrow is comparatively easy to access, and stem cells can be collected in a short, minimally invasive procedure.

Laboratory and preclinical research suggests that stem cells may play a role in healing and tissue regeneration processes. This is being investigated in early clinical research in moderate to severe osteoarthritis, tendon injuries and other orthopedic problems.

A BMC therapy is the injection of your own bone marrow concentrate at the site of the problem, for example into a joint, at a tendon, into the spine or into the erectile tissue. It takes place during one visit of two days. BMC is experimental: there is no marketing authorisation for this use. At ANOVA IRM it is given as an individual treatment attempt (individueller Heilversuch), after a personal medical assessment and with your informed consent. Read more about the regulatory status of ANOVA IRM.

ANOVA IRM offers two products made from your own cells. BMC contains living cells and is applied once at the site of the problem. The MSC secretome (MSEC) is cell-free and is suited to repeated applications. Which product is medically suitable is decided for each patient.

• Autologous: from your own body; donor and recipient are the same person.
• Iliac crest: the upper edge of the pelvic bone, from which the bone marrow is collected.
• Hematopoietic stem cells: blood-forming stem cells of the bone marrow.
• Mesenchymal stem cells (MSC): stem cells of the connective tissue that can develop into bone, cartilage and fat cells in the laboratory ^[5],[11].
• Intra-articular: into the joint. Intradiscal: into the intervertebral disc. Intracavernous: into the erectile tissue of the penis.
• Individual treatment attempt (individueller Heilversuch): the use of a medicine without marketing authorisation for an individual patient, after full disclosure and consent.

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In this section:

• Experimental — and Fully Legal, Manufactured Under GMP
• How Safe Is ANOVA BMC?
• Bone Marrow From the Pelvic Bone Used by ANOVA
• How BMC Is Produced
• Quality Control and Release of BMC
• Routes of Administration
• Individual Treatment Plans and Cost
• Who Qualifies for BMC Treatment, and What Are the Requirements?
• What Does BMC Therapy at ANOVA IRM Involve, Step by Step?
• Frequently Asked Questions — Production and Treatment

ANOVA IRM holds a procurement authorisation for bone marrow (Section 20b AMG) and a manufacturing authorisation for BMC (Section 13 AMG). Our manufacturing is therefore subject to ongoing supervision by the competent authority, the Hessian State Office for Health and Care (HLfGP). This means that our products are manufactured under regulated and regularly inspected conditions. BMC has no marketing authorisation. It is given as an individual treatment attempt (individueller Heilversuch) after full disclosure and with your consent, and only to our own patients. Why this is legal is explained on our page on the regulatory status of ANOVA IRM.

Manufacturing under an official authorisation adds a layer of safety. The competent authority inspects the facility every two years, and every change to the manufacturing process and every new material must be reported to it. Providers without an authorisation are not subject to this control.

ANOVA has employed BMC as a non-surgical regenerative treatment for different applications, with focus in orthopedics. BMC has been made with the same process since 2012. After a pause from 2017 because of a change in German law, it has been manufactured again since 2019 under a manufacturing authorisation according to Section 13 AMG. Since then, 153 people have been treated with it. As of October 2026, BMC has not caused a serious adverse event. In clinical research, safety is first examined in phase 1/2 studies with roughly 10 to 100 patients. ANOVA IRM has not conducted such a study, but the number of people treated is well above that. Talk to our experienced and knowledgeable physicians today, to learn more about your treatment options at ANOVA.

BMC comes from your own body, so no infection can be transmitted from a donor and there is no reaction against foreign cells. The cells are not multiplied, which avoids the risks of long culture. The safety of BMC also depends on the quality of manufacture; this is why quality control takes place before every application. What the medicines regulators say about the safety of stem cell therapy is set out under unproven therapies.

No medical treatment is free of risk. With BMC, the risks come mainly from the two procedures: the collection of bone marrow from the pelvic bone and the injection at the site of treatment. Bleeding, pain at the puncture site and infection are possible. In a survey of more than 19,000 diagnostic bone marrow procedures in the United Kingdom, adverse events were reported in 0.08 %, most often bleeding ^[1]. Your doctor explains the risks to you before treatment.

ANOVA IRM collects bone marrow from the back of the pelvic bone (iliac crest). The collection takes place under local anaesthesia and brief sedation; an anaesthesiologist looks after you, with the aim of keeping it as pain-free as possible. The bone marrow is drawn with a needle and syringe and passed directly to our facility in the same building.

BMC is produced on the day of collection in our own facility in Offenbach, under a procurement authorisation (Section 20b AMG) and a manufacturing authorisation (Section 13 AMG). The whole procedure takes place on the same day:

• Step 1 — Collection: bone marrow is collected from the pelvic bone under local anaesthesia and brief sedation.
• Step 2 — Concentration: in a closed system, part of the blood serum and of the red blood cells is removed, so that the cells are contained in a smaller volume. The cells are not cultured or multiplied.
• Step 3 — Quality control: the tests required before application are carried out, and a sample for microbiological testing is taken.
• Step 4 — Application: BMC is injected at the site of treatment on the same day.

BMC is not frozen, because freezing can reduce the desired properties of stem cells ^[7]. It is applied directly after production and testing.

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All tests follow GFP/GMP requirements and have been approved and inspected by the competent authority. Methods follow the European Pharmacopoeia (Ph. Eur.) where applicable. Unlike MSEC, part of the quality control of BMC takes place on the day of treatment before the application, and the microbiological control is completed afterwards, because its result takes seven days. BMC is a special product because it is not substantially processed.

The procedure for BMC is very short, and the product is not cultured and not openly manipulated. So the chance of contamination is low but present. As the product cannot be frozen, the result of the microbial growth test is only ready after application, as for all other cellular stem cell products that cannot be frozen. In contrast, ANOVA MSEC can be frozen. ANOVA has treated patients with BMC since 2012, and no severe side effects due to contamination have happened since.

If the microbial growth test is positive, the patient is informed and treated if necessary. Since 2012 this has never been necessary.

Some tests are not needed for BMC, for the following reasons:

• Endotoxin: no test necessary, because all materials used are endotoxin-tested.
• Potency or a suitable surrogate parameter: no test necessary, because BMC is applied directly, is only minimally processed, is not cultured and keeps its natural composition; its shelf life would be exceeded before assay results were available.
• Purity and cell composition: no test necessary, because BMC is only minimally processed; the composition corresponds to the individual composition of your bone marrow.

BMC is always applied locally, at the site of the problem, and never into a vein. Because it contains blood cells, BMC is not given intrathecally (into the cerebrospinal fluid). Where needed, the injection is guided by imaging such as CT or ultrasound.

Into the joint (intra-articular) — osteoarthritis and joint injuries

BMC is injected into the affected joint, so that it reaches the inflamed joint lining and the cartilage directly. CT guidance is sometimes used in the hip and shoulder, rarely in the knee. Several joints can be treated during the same visit, usually with a double BMC. More on osteoarthritis and joint injuries.

At tendons and ligaments (periarticular)

For tendon and ligament injuries, BMC is injected at the injured structure next to the joint, for example at the rotator cuff, the Achilles tendon or the elbow (tennis elbow).

Spine — disc, facet joints, vertebral bodies and ligaments

For back and neck pain, BMC is injected under CT guidance into the inflamed disc, facet joint, vertebral body or spinal ligament. Several segments can be treated during the same visit. More on back pain and spine conditions.

Into the erectile tissue (intracavernous) — erectile dysfunction

For erectile dysfunction, a urologist places the needle and an ANOVA IRM physician injects BMC into the erectile bodies. More on erectile dysfunction.

Treatment with BMC costs approximately €8,000 to €9,000 and is billed according to the German Medical Fee Schedule (GOÄ). It takes one visit of two consecutive days, with bone marrow collection and injection on the same day. Where CT guides the injection, for example always in the lumbar spine, the cost is closer to €9,000. Treating several joints or areas in one visit usually requires a double BMC, which costs correspondingly more. Before any decision you receive an individual written estimate. Travel and accommodation are not included. All prices are subject to change. Our blog post How much does stem cell therapy cost? explains what drives the cost of stem cell treatment in general.

Many of the conditions treated with BMC are chronic. BMC is intended to modify their course, not to cure them, so a treatment may need to be repeated after assessment. A repeat requires a new bone marrow collection.

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BMC may be considered for adults with one of the conditions listed in the introduction above, after a full diagnostic work-up, when the source of the problem can be treated locally. Requirements are fitness for the brief sedation used for the bone marrow collection and a blood test before travel. Our stem cell treatments are experimental, but we only treat patients for whom we believe the risk/benefit ratio indicates treatment based on the state of the art, i.e., medical, scientific evidence.

What Are the Contraindications for BMC Treatment?

Please understand that we therefore do not treat patients for whom the following points apply:

• Active cancer in the last two years
• Not yet of legal age
• Existing pregnancy or lactation period
• Unable to breathe on own, ventilator (sedation for the bone marrow collection)
• Difficulty breathing in supine position (sedation for the bone marrow collection)
• Dysphagia (extreme difficulty swallowing)
• Psychiatric disorder
• Active infectious disease (Hepatitis A, B, C, HIV, Syphilis, or other)

In the schema below we have summarized the steps towards your individual BMC therapy from initial free-of-charge consultation with our patient care managers up to the final BMC application in Offenbach, Germany.

What Screening Is Needed Before You Travel?

Before you travel, a preliminary screening in your home country helps to avoid an unnecessary journey. This is usually a blood test for medical or infectious reasons against treatment, together with your existing findings and images.

What Happens During Your Visit to Offenbach, Germany?

You spend two consecutive days in Offenbach as an outpatient, less than 20 minutes from Frankfurt Airport. On day one, your doctor explains the treatment, obtains your consent and takes blood; an MRI can be added if useful. On day two, bone marrow is taken from the pelvic bone under brief sedation, and BMC is injected on the same day. ANOVA IRM carries out the full donor screening required under EU GMP and the German AMWHV (Arzneimittel- und Wirkstoffherstellungsverordnung). Your blood is analysed in a contract laboratory that holds the corresponding GMP/GFP licences. This is why you arrive one day before the treatment. ANOVA IRM treats only patients without an infectious disease.

How Is Your BMC Produced and Quality-Controlled?

BMC is prepared on the day of collection in our own facility. The bone marrow is concentrated but not multiplied in the laboratory. Key quality tests are completed before the injection; the microbiological control follows afterwards (see Quality Control and Release of BMC).

How Often Is BMC Applied?

Usually once, on the second day of the visit. Several joints or segments can be treated during the same visit. A repeat after assessment requires a new visit and a new bone marrow collection.

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In this section:

• BMC Therapy – What Current Research Suggests
• The Story of BMC Therapy
• The History of Bone Marrow Concentrate
• Are Studies of Bone Marrow Products Evidence for BMC?
• How BMC May Work in Each Condition
• Frequently Asked Questions — Evidence

Bone Marrow Concentrate (BMC) contains growth factors and cells that are the subject of regenerative medicine research. It contains multipotent cells, which in laboratory research are able to develop into several different cell types. The detailed mechanisms of stem cell action are not well understood. Laboratory and preclinical findings indicate that stem cells may influence immune and inflammatory processes and may be involved in regeneration processes.

Results differ by condition. In heart disease, Cochrane reviews of bone marrow cell treatments found no proven benefit: in acute heart attack no effect on survival ^[43], in chronic heart disease only low-quality evidence ^[44]. In orthopaedic conditions such as osteoarthritis, small external studies reported less pain and better function, while placebo-controlled studies could not yet demonstrate a benefit ^{[16],[19],[26]}. Interestingly, research suggests that the previously less studied blood cells of the bone marrow may play a role in healing processes. They contain cells with CD34+ and c-kit surface markers, to which research attributes a role in the repair of damaged tissue.

Early research in stem cells has focused on investigating the regenerative capabilities of embryonic or adult Mesenchymal Stem Cells. While scientists and doctors still hope they can use these cells for the treatment of many diseases, they cannot be used for treating patients in most countries, due to legal restrictions and safety concerns.

Therefore, doctors and scientists began searching for alternatives within this research field. Bone marrow stem cells are one such alternative. They are comparatively abundant and relatively easy to access, and both the harvest and the application are minimally invasive. In orthopaedics, concentrated bone marrow from the iliac crest was used early on to support bone healing, for example in fractures that did not heal (non-unions) ^[28].

For many years, critics of stem cell treatments claimed that bone marrow stem cells are not effective, because they mainly contain blood forming cells and only a low number of Mesenchymal Stem Cells (MSCs). However, ongoing research suggests that the broader mixture of cells and signaling factors found in bone marrow may nevertheless contribute to regenerative effects ^[24].

Concentrated bone marrow has been used in orthopaedics for more than 20 years. In 2002, a French team reported on 189 hips in 116 patients with bone death in the head of the thigh bone (osteonecrosis of the femoral head), treated with concentrated bone marrow from the iliac crest and followed for 5 to 10 years. Of the 145 hips treated before the head of the bone collapsed, 9 later needed a hip replacement ^[27]. In 2005, the same team reported that 53 of 60 fractures that had not healed (non-unions) healed after concentrated bone marrow ^[28].

In the following years, many orthopaedic surgeons also used BMC in joints, and external studies reported good results. In 15 patients with deep cartilage lesions of the knee, treated in a single operation with BMC and a collagen membrane, all scores had improved significantly after 2 years, without a control group ^[20]. In 2016, a systematic review of 11 external studies of the knee found good to excellent overall results in all of them, but also a lack of high-quality studies ^[23]. An external registry of 18 clinics recorded 3,012 procedures in 2,372 patients from 2005 to 2014; the rate of adverse events was lowest in patients who received BMC alone ^[2].

For many years, orthopaedic surgeons in Germany prepared and used bone marrow concentrate in their practices without an official authorisation. Two changes to the German Medicines Act (AMG) ended this. In 2009, advanced therapy medicinal products were excluded from preparation without authorisation, and in 2012 the exemption for tissue preparations in Section 20d AMG was restricted, so that an authorisation became necessary. An authorisation requires a production facility that meets good manufacturing practice (GMP), qualified staff, documented quality control and regular inspections by the authority. Many doctors did not want to take on this considerable effort and stopped offering BMC. ANOVA took the demanding route of obtaining these authorisations and manufacturing under GMP. How the authorisations of ANOVA IRM fit together is explained above.

Only in part. Studies use different bone marrow products: concentrated bone marrow (BMC or BMAC), isolated mononuclear cells (BM-MNC) and mesenchymal stem cells multiplied in the laboratory (BM-MSC). They are prepared, dosed and applied differently. Results for cultured BM-MSC do not directly apply to BMC, and results for BMC from another provider apply to BMC at ANOVA IRM only to a limited extent.

Most clinical studies of BMC are small, and only a few have a control group. Reviews describe mostly positive but inconsistent results and call for larger randomised studies ^{[23],[24],[26]}. The American Academy of Orthopaedic Surgeons considers the evidence for concentrated bone marrow in knee osteoarthritis to be limited ^[25]. ANOVA IRM has not yet tested BMC in a clinical study.

In many of the conditions treated with BMC, chronic inflammation contributes to pain and to ongoing tissue damage. BMC is intended to dampen this inflammation at the site of the problem and to support repair. The following sections summarise the rationale for each condition; the full rationale is on the disease pages.

Osteoarthritis

In osteoarthritis, inflammation of the joint lining drives pain and cartilage loss. Injected into the joint, BMC is intended to reduce this inflammation first and to slow the progression of the disease. In an external retrospective study of 121 patients with advanced knee osteoarthritis, pain fell after a single BMC injection, without a control group ^[19]. In one small external placebo-controlled study of 25 patients, reported after 6 and 12 months, a benefit of BMC over saline could not yet be demonstrated ^[16],[17]. Further external studies are listed below ^[18],[21]. The full rationale for BMC in osteoarthritis is on our osteoarthritis page.

Joint, tendon and ligament injuries

After an injury, inflammation at the tendon, ligament or joint often causes the pain. BMC injected at the injured structure is intended to calm this inflammation and to support repair. In an external registry of 102 patients with shoulder osteoarthritis or rotator cuff tears, pain and function improved after BMC, without a control group ^[22]. A review describes the repair of tendons and ligaments with bone marrow cells mainly from animal studies ^[30]. The full rationale for BMC in joint injuries is on our joint injuries page.

Back pain and spine

Back pain often arises where a disc, facet joint, vertebral body or spinal ligament is inflamed. BMC injected at this site is intended to dampen the inflammation and the pain. In small external studies of discogenic back pain, pain fell after BMC injected into the disc, with follow-up of up to three years and without a control group ^{[31],[32],[33]}. The full rationale for BMC in back pain and spine conditions is on our back pain and spine conditions page.

Erectile dysfunction

In most men with erectile dysfunction, the blood vessels, nerves and smooth muscle of the erectile tissue are affected. BMC injected into the erectile bodies is intended to support this tissue. Small external early studies with bone marrow cells mainly examined safety; some reported better erectile function, without a control group ^{[34],[35],[36]}. The full rationale for BMC in erectile dysfunction is on our erectile dysfunction page.

Rheumatoid arthritis

In rheumatoid arthritis, the immune system attacks the lining of the joints. BMC can additionally be injected into individual affected joints, with the aim of reducing local inflammation and pain; treatment by a rheumatologist remains the basis. The full rationale for BMC in rheumatoid arthritis is on our rheumatoid arthritis 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 are stem cells?
• What is MSC secretome (MSEC)?
• Which conditions do we treat?

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ANOVA IRM shares its premises in Offenbach with two further institutions owned by Dr. Stehling: the Prof. Dr. Stehling Institut für Bildgebende Diagnostik GmbH, providing MRI and CT imaging, and the VITUS PRIVATKLINIK Prof. Dr. Stehling GmbH. Because imaging is carried out in the same building, diagnostics can be performed in-house rather than referred elsewhere. See diagnostics at ANOVA IRM.

This page is the reference home for literature on bone marrow concentrate. Other pages link here rather than repeating the list.

General — bone marrow concentrate, cells and collection

Other clinical studies and reviews of clinical studies

• [1] Bain BJ. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol. 2005;58(4):406–408. doi:10.1136/jcp.2004.022178. PMID: 15790706. PMCID: PMC1770618.
• [2] Centeno CJ, Al-Sayegh H, Freeman MD, et al. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop. 2016;40(8):1755–1765. doi:10.1007/s00264-016-3162-y. PMID: 27026621. Correction: Int Orthop. 2018;42(1):223. PMID: 29110069.
• [3] Caradonna E, Mormone E, Centritto EM, et al. Different methods of bone marrow harvesting influence cell characteristics and purity, affecting clinical outcomes. JVS Vasc Sci. 2023;4:100130. doi:10.1016/j.jvssci.2023.100130. PMID: 38058747. PMCID: PMC10696233.
• [4] Mantripragada VP, Boehm C, Bova W, et al. Patient age and cell concentration influence prevalence and concentration of progenitors in bone marrow aspirates: an analysis of 436 patients. J Bone Joint Surg Am. 2021;103(17):1628–1636. doi:10.2106/JBJS.20.02055. PMID: 33844657.

Systematic reviews and guidance

• [5] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317. doi:10.1080/14653240600855905. PMID: 16923606.
• [6] Cavallo C, Boffa A, Andriolo L, et al. Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. Int Orthop. 2021;45(2):525–538. doi:10.1007/s00264-020-04703-w. PMID: 32661635. PMCID: PMC7843474.
• [7] Bahsoun S, Coopman K, Akam EC. The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review. J Transl Med. 2019;17(1):397. doi:10.1186/s12967-019-02136-7. PMID: 31783866.
• [8] Patel K, Siltamäki VE, Ben RN, Pineault N. Evolution in the cryopreservation of hematopoietic stem cells. Exp Hematol. 2026;163:105873. doi:10.1016/j.exphem.2026.105873. PMID: 42660306.

Animal studies

• [9] Singer J, Nishimura H, Xiao Z, et al. Short-term cryopreservation preserved the function of MSCs from bone marrow aspirate concentrate. Cells. 2025;14(19):1569. doi:10.3390/cells14191569. PMID: 41090796. PMCID: PMC12524150.

Laboratory studies

• [10] Cassano JM, Kennedy JG, Ross KA, et al. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. Knee Surg Sports Traumatol Arthrosc. 2018;26(1):333–342. doi:10.1007/s00167-016-3981-9. PMID: 26831858.
• [11] Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147. doi:10.1126/science.284.5411.143. PMID: 10102814.
• [12] Ragni E, Taiana M, Visconte C, et al. Side-to-side characterisation of cellular content, soluble factors and in vitro potential on chondrocytes for bone marrow aspirate concentrate and adipose-derived stromal vascular fraction. J Exp Orthop. 2025;12(2):e70254. doi:10.1002/jeo2.70254. PMID: 40357029. PMCID: PMC12066993.
• [13] Ruoss S, Nasamran CA, Ball ST, et al. Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues. Sci Adv. 2024;10(28):eadn2831. doi:10.1126/sciadv.adn2831. PMID: 38996032. PMCID: PMC11244553.
• [14] Moll G, Alm JJ, Davies LC, et al. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells. 2014;32(9):2430–2442. doi:10.1002/stem.1729. PMID: 24805247. PMCID: PMC4381870.
• [15] François M, Copland IB, Yuan S, et al. Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-γ licensing. Cytotherapy. 2012;14(2):147–152. doi:10.3109/14653249.2011.623691. PMID: 22029655. PMCID: PMC3279133.

Osteoarthritis and joints

Other clinical studies and reviews of clinical studies

• [16] Shapiro SA, Kazmerchak SE, Heckman MG, et al. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med. 2017;45(1):82–90. doi:10.1177/0363546516662455. PMID: 27566242.
• [17] Shapiro SA, Arthurs JR, Heckman MG, et al. Quantitative T2 MRI mapping and 12-month follow-up in a randomized, blinded, placebo controlled trial of bone marrow aspiration and concentration for osteoarthritis of the knees. Cartilage. 2019;10(4):432–443. doi:10.1177/1947603518796142. PMID: 30160168.
• [18] Goncars V, Kalnberzs K, Jakobsons E, et al. Treatment of knee osteoarthritis with bone marrow-derived mononuclear cell injection: 12-month follow-up. Cartilage. 2019;10(1):26–35. doi:10.1177/1947603517746721. PMID: 29373926. PMCID: PMC6376566.
• [19] Themistocleous GS, Chloros GD, Kyrantzoulis IM, et al. Effectiveness of a single intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with grade 3 and 4 knee osteoarthritis. Heliyon. 2018;4(10):e00871. doi:10.1016/j.heliyon.2018.e00871. PMID: 30364761.
• [20] Gobbi A, Karnatzikos G, Scotti C, et al. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up. Cartilage. 2011;2(3):286–299. doi:10.1177/1947603510392023. PMID: 26069587. PMCID: PMC4300809.
• [21] Centeno C, Pitts J, Al-Sayegh H, et al. Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. Biomed Res Int. 2014;2014:370621. doi:10.1155/2014/370621. PMID: 25276781.
• [22] Centeno CJ, Al-Sayegh H, Bashir J, et al. A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res. 2015;8:269–276. doi:10.2147/JPR.S80872. PMID: 26089699. PMCID: PMC4463777.

Systematic reviews and guidance

• [23] Chahla J, Dean CS, Moatshe G, et al. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sports Med. 2016;4(1):2325967115625481. doi:10.1177/2325967115625481. PMID: 26798765.
• [24] Kim GB, Seo MS, Park WT, et al. Bone marrow aspirate concentrate: its uses in osteoarthritis. Int J Mol Sci. 2020;21(9):3224. doi:10.3390/ijms21093224. PMID: 32370163.
• [25] American Academy of Orthopaedic Surgeons. Concentrated Bone Marrow Aspirate for Knee Osteoarthritis: Technology Overview. Rosemont, IL: AAOS; adopted 3 December 2021. https://www.aaos.org/globalassets/quality-and-practice-resources/biologics/technology-overview-concentrated-bone-marrow-aspirate-for-knee-osteoarthritis.pdf
• [26] Park D, Koh HS, Choi YH, et al. Bone marrow aspirate concentrate (BMAC) for knee osteoarthritis: a narrative review of clinical efficacy and future directions. Medicina (Kaunas). 2025;61(5):853. doi:10.3390/medicina61050853. PMID: 40428811.

Tendons, ligaments and bone

Other clinical studies and reviews of clinical studies

• [27] Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;(405):14–23. doi:10.1097/00003086-200212000-00003. PMID: 12461352.
• [28] Hernigou P, Poignard A, Beaujean F, Rouard H. Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am. 2005;87(7):1430–1437. doi:10.2106/JBJS.D.02215. PMID: 15995108.
• [29] Hernigou P, Guissou I, Homma Y, et al. Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes. Int Orthop. 2015;39(8):1639–1643. doi:10.1007/s00264-015-2738-2. PMID: 25795249.

Systematic reviews and guidance

• [30] Kushida T, Iida H. Bone marrow cell transplantation efficiently repairs tendon and ligament injuries. Front Cell Dev Biol. 2014;2:27. doi:10.3389/fcell.2014.00027. PMID: 25364734. PMCID: PMC4207000.

Back pain and spine

Other clinical studies and reviews of clinical studies

• [31] 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.
• [32] 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.
• [33] 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.

Erectile dysfunction

Phase 1 and 1/2 trials

• [34] Bieri M, Said E, Antonini G, et al. Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction. J Transl Med. 2020;18(1):24. doi:10.1186/s12967-019-02195-w. PMID: 31937310. Manufacturer involvement: one author affiliation is Creative Medical Health, San Diego, which offers the CaverStem procedure studied; no control group.
• [35] Yiou R, Hamidou L, Birebent B, et al. Safety of intracavernous bone marrow-mononuclear cells for postradical prostatectomy erectile dysfunction: an open dose-escalation pilot study. Eur Urol. 2016;69(6):988–991. doi:10.1016/j.eururo.2015.09.026. PMID: 26439886.
• [36] Yiou R, Hamidou L, Birebent B, et al. Intracavernous injections of bone marrow mononucleated cells for postradical prostatectomy erectile dysfunction: final results of the INSTIN clinical trial. Eur Urol Focus. 2017;3(6):643–645. doi:10.1016/j.euf.2017.06.009. PMID: 28753830.

Other conditions: heart, liver, spinal cord and ALS

Phase 1 and 1/2 trials

• [37] Heldman AW, DiFede DL, Fishman JE, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014;311(1):62–73. doi:10.1001/jama.2013.282909. PMID: 24247587. PMCID: PMC4111133.
• [38] Yoon SH, Shim YS, Park YH, et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: phase I/II clinical trial. Stem Cells. 2007;25(8):2066–2073. doi:10.1634/stemcells.2006-0807. PMID: 17464087.

Other clinical studies and reviews of clinical studies

• [39] Terai S, Ishikawa T, Omori K, et al. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006;24(10):2292–2298. doi:10.1634/stemcells.2005-0542. PMID: 16778155.
• [40] Lyra AC, Soares MB, da Silva LF, et al. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol. 2007;13(7):1067–1073. doi:10.3748/wjg.v13.i7.1067. PMID: 17373741. PMCID: PMC4146869.
• [41] am Esch JS 2nd, Knoefel WT, Klein M, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. 2005;23(4):463–470. doi:10.1634/stemcells.2004-0283. PMID: 15790766.
• [42] Prabhakar S, Marwaha N, Lal V, et al. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. Neurol India. 2012;60(5):465–469. doi:10.4103/0028-3886.103185. PMID: 23135021.

Systematic reviews and guidance

• [43] Fisher SA, Zhang H, Doree C, et al. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2015;2015(9):CD006536. doi:10.1002/14651858.CD006536.pub4. PMID: 26419913. PMCID: PMC8572033.
• [44] Fisher SA, Doree C, Mathur A, et al. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst Rev. 2016;12(12):CD007888. doi:10.1002/14651858.CD007888.pub3. PMID: 28012165. PMCID: PMC6463978.

Animal studies

• [45] Rodriguez-Menocal L, Shareef S, Salgado M, et al. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing. Stem Cell Res Ther. 2015;6(1):24. doi:10.1186/s13287-015-0001-9. PMID: 25881077. PMCID: PMC4414366.