Avoid surgery - fasten recovery
Stem Cell-based Therapy for Knee Injuries and Degeneration

Both knee injuries and knee degeneration are frequently reported conditions, and have very limited effective therapy options. Regenerative and cellular therapies for knee pain are urgently needed, both for the treatment of knee injuries, and age-related degenerative knee problems. Treatment of problems related to the knee are among the most applied and researched fields for stem cell-based therapies.

ANOVA offers a unique program with Stem Cell Secretome in combination with Bone Marrow Concentrate Stem Cell injections. Our therapy programs are based on your individual needs and designed for your optimal regenerative effect. Our German Stem Cell Clinic in the heart of Europe offers easy access to patients from all over the world. Contact us today to find out more about your treatment options.

On this page we inform you about knee injuries like meniscus, tondon and ligament injuries, degenerative knee conditions, cartilage damage etc. covering an overview on important aspects of causes, treatment options, precision diagnostics that reveals the cause of pain and location of the pain-causing defect, as well as our stem cell-based therapies that we offer in Offenbach (near Frankfurt/Main) Germany.

Jump directly to the following topics:

We treat the following injuries and conditions:.

  • Arthritis
  • Meniscus Tear
  • ACL, MCL, PCL or LCL sprain or tear
  • Patellofemoral Syndrome / Chondromalacia
  • Pes anserine bursitis, Baker’s cyst and others
  • Patellar tendonitis, Hamstrings Tendinopathy and Biceps Femoris Insertional Tendinopathy

Generally Available Conventional Therapies

Knee operations should always be considered as the last option for treatment, after the careful review of the results obtained from diagnostics, and after all conventional and regenerative options have been exceeded. Many studies have shown significant improvement of knee function and reduction of pain with the use of stem cell-based therapies.

Stem cell treatments for Knee injuries and degeneration at
ANOVA Institute for Regenerative Medicine - Offenbach, Germany
BMC, Secretome/Exosomes, PRP

Potency Hypothesis of Stem Cell Therapies

Stem cells possess the potential to communicate with the immune cells that elicit the inflammation and by natural, so far not understood mechanisms may inhibit this immune-over-reaction. Furthermore, stem cells have the ability to stimulate regeneration of tissue thereby counteracting the wear and loss of cartilage in the affected joints. Negative long-term effects similar to cortisone are not expected. The aim of a stem cell treatment is therefore, the fast relief of pain, the slowing of the disease progression and in the best cases to even support joint regeneration. This can dramatically increase the quality of life, especially for patients with severe pain, as well as the movement duration and range.

Two Targeted Effects: Pain Relief and Progression Improvement

A stem cell treatment can elicit two effects in affected joints that build on one another. Due to the modulation of the underlying immune reaction the stem cell injection decreases or even stops the inflammation. As inflammation, especially in early stages, often is the main cause of pain, targeted stem cell injection often results in immediate pain relief up to complete pain-free movements of the treated joint.

The effects on disease progression builds on the inhibition of inflammation. Upon the halting of the inflammation the joint returns to a resting-phase and regeneration and healing can start. With adequate on-going therapy in combination with e.g. physiotherapy, regeneration of cartilage and partially torn tendons and ligaments can take place. As all effects are patient- and disease stage-dependent and may be influenced by additional, external factors, we always apply individual treatment plans.

BMC - Bone Marrow Concentrate - Autologous

Autologous (self) BMC are our main therapy option for locally-restricted knee injuries and degeneration. In such cases we treat patients with targeted, localized BMC injections. BMC contains autologous meaning patients own, adult  stem cells (hematopoietic and mesenchymal stem cells in natural composition) which we isolate and concentrate from your pelvis crest in a short process under slight sedation.

These stem cells are supposed to inhibit the inflammation thereby relieving you from pain and to stimulate regeneration of the meniscal cartilage or the injured tendons. For an on-going therapy, we combine BMC with PRP (platelet-rich plasma) or Hyaluronic Acid (see below). More information about this type of stem cell therapy is summarized on our page an BMC.

BMC-bone-marrow-concentrate-therapy | Germany

BMC - bone marrow concentrate
ANOVA IRM - Germany

PRP - Platelet-Rich Plasma - Autologous

PRP is a comparably inexpensive experimental therapy as platelets (thrombocytes  naturally containing growth factors and stimulants) are isolated from autologous (own) blood without isolation of stem cells.

For knee injuries, we use PRP often in combination with BMC and is administered in-between BMC treatments to continuously support the anti-inflammatory effect. Besides this, PRP is well-known as a stimulant for wound healing in e.g. paradontits therapy or as a measure against hair loss.

More on PRP (as a combination therapy) is summarized on our PRP overview page.

PRP-platelet-rich-plasma-therapy | Germany

PRP - platelet-rich plasma
ANOVA IRM - Germany

Hyaluronic Acid - HA

Another, cost efficient supportive treatment is injection of hyaluronic acid into the knee cavity. 

Especially in early cases, this can reduce pain and result in a better "lubrication" of the knee. Bone parts do not crunch directly on another after HA injection.

Hyaluronic acid alone, on the other hand, is not expected to have regenerative effects on the damaged cartilage or bone.

Therefore, we usually combine HA with BMC treatment and HA is given intermittendly between BMC treatments.

HA - Hyaluronic acid | Germany

Hyaluronic acid - HA
ANOVA IRM - Germany

MSEC - Mesenchymal Stem Cell Secretome - Exosomes - Autologous

Usually knee conditions are not treated with MSEC.

Secretome/Exosomes is a product that we use for systemic administration in primarily inflammatory diseases such rheumatoid arthritis or in cases of poly-osteoarthritis where more than a few joints are affected. .

MSC-secretome-exosome-therapy | Germany

MSC secretome - exosome - therapy
ANOVA IRM - Germany


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.

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
  • Difficulty breathing in supine position
  • Dysphagia (extreme difficulty swallowing)
  • Psychiatric disorder
  • Active infectious disease (Hepatitis A, B, C, HIV, Syphilis, or other)

How does the ANOVA Therapy Differ?
Diagnostics – We Look for the Cause of Your Pain

Prof. Dr. Dr. Dr. M. K. Stehling, the founder of ANOVA IRM and the Vitus Prostate Center , is a radiologist (MD) and holds a PhD in physics. For this reason, the ANOVA Institute for Regenerative Medicine, in cooperation with the Prof. Stehling Institute for Diagnostic Imaging located in the same building, has the capability to use special precision diagnostics such as arthro-MRI and non-radioactive contrast MRIs.

Compared to many conventional MRIs, these methods are often able to localize the pain-causing inflammation, degeneration and damage in your knee. This enables us to determine individually how patients should be treated and where the stem cells should be applied.

Furthermore, in consultation with you and if advisable, we supplement our patient-specific diagnostics with specific blood tests on hormones, inflammation parameters and other factors that are important in your case, or recommend further examinations such as a preventive MRI spinal scan.

ANOVA IRM Deutschland Diagnostik MRT Schmerzen Ganzkörper Scan Siemens

Precision MRI scans - find the source of pain
ANOVA IRM © Siemens Healthcare GmbH

How Does the ANOVA Therapy Differ?
We Implant the Stem Cells Precisely Where They are Needed

CT-assisted stem cell injection into joints | ANOVA

CT-assisted stem cell injection into joints
ANOVA IRM © Siemens Healthcare GmbH

Based on our specific diagnostics using arthro-MRI and non-radioactive contrast medium MRIs, we can, in contrast to many other clinics, deliver the stem cells with image support, e.g. using CT, precisely to the affected area. This means we can inject into and at the knee cavity as well as tendons/ligaments to specifically and quickly trigger an effect where inflammation causes pain. All interventions are performed under supervision and care of our anesthesiologist and are pain free.

A purely intravenous administration, as many other clinics do, is only performed for the secretome (exosomes) if this is to be used to treat chronic inflammatory conditions of the knee.

Of course, we will thoroughly advise you in the early process and the on-site consultation in advance on all steps and discuss alternatives and expectations.

© https://www.researchgate.net/publication/342249238_Image_guided_sacroiliac_joint_corticosteroid_injections_in_children_an_18-year_single-center_retrospective_study

Are you interested but Uncertain?
Book a Counselling Appointment!

Our patient care managers are happy to inform you about what information we need upfront (MRI, CT, X-ray), how to transfer large data files and schedule a counseling appointment with our physicians for you. Our patient care managers are happy to inform you about what information we need upfront, how to transfer large data files and schedule a counseling appointment with our physicians for you. Please use our contact form to support a fast processing of your case and request.

You are also always welcome to send us an e-mail about your case. The counseling appointment may also take place per telephone or video chat if you live outside Germany. For more intense counseling or additional diagnostic evaluations you may also book an on-site appointment. We can perform needed MRI on the same day. All services rendered by our patient care team are free of charge and we inform you about all physician appointment charges up-front.

Avoid joint replacement implants in Osteoarthritis | ANOVA IRM

Avoid joint replacement with stem cell therapy
ANOVA IRM - Germany

Therapy Workflow for Knee Injuries and Degeneration

The precise workflow is described in detail on the stem cell- specific pages of BMC (most often used for OA), Secretome/Exosomes und PRP (as combination therapy).

All therapies are divided into phases such as evaluation of the medical history (we analyze your current therapies and medical records), initial counselling and evaluation of potential, patient-individual benefit of a stem cell therapy (indication statement), preliminary examinations, diagnostics, consultation on all therapy options, preparation of an individual treatment plan including cost estimate, harvesting of tissue, production of the stem cell product, quality control of the product and application. There are two special features for knee-osteoarthritis and rheumatoid arthritis patients. If your previous findings have not found the specific causes of your joint pain, we will examine you in advance with a precise and informative arthro-MRI or an MRI with non-radioactive contrast medium, if you wish. In addition, we often apply the stem cells (BMC) intra-articularly (i.e., directly in the joint). This means that we deliver the stem cells to the exact location where your pain originates.

Unfortunately, according to the risk-benefit ratio, we cannot treat children or pregnant women. In addition, other factors can also be exclusion criteria.

How Long Does a Stem Cell Therapy Take?

The initial analyses and counselling can be done without you having to travel to Offenbach (near Frankfurt/Main, Germany). This period can be 2 weeks up to months depending on the availability of patients slots. If you live further away, we will conduct the initial discussions by telephone or video conference. For the actual treatment, you will travel to Offenbach. Then, depending on the therapy, the tissue collection, quality control and treatment type it will take as follows:

BMC- und PRP Therapy

Each donation and application of BMC (most often used for knee treatment) and PRP (as combination therapy) on-site period: 2 days (consecutive days).

Secretome/Exosome Treatment:

Preparation and harvest of the fat (mini-liposuction) need once 2 days (consecutive days) in Offenbach, followed by enrichment of the mesenchymal stem cells (Secretome/Exosome) and quality control.

Approximately 4 weeks after the isolation, the therapy begins according to the therapy plan determined with you. You will then come to Offenbach am Main (Germany) several times for the application. The shelf life of the secretome (exosomes) is 2 years.

How Much Does Stem Cell Treatment for Knee Injuries Cost?

Our treatments are always tailored to your specific situation, disease, stage and other factors. The therapies differ in the product used (BMC, secretome, PRP or hyaluronic acid), the frequency of treatment as well as the further examinations and your sedation and anesthesia wishes. A treatment for knee injuries or knee degeneration can cost from a few hundred to several thousand euros. You will receive a cost estimate for all treatments in advance so that you can accurately estimate what a treatment would cost in your individual case.

Does my Health Insurance Cover the Therapy Costs?

Unfortunately, at the moment it is assumed that health insurance companies do not cover the costs of experimental therapies (BMC, secretome, PRP, micro-fracture technique), i.e. you will have to bear the costs entirely yourself.

Other Important Therapy Strategies for Knee Injuries and Degeneration

Osteoarthritis is a chronic progressive diseases. Therefore, it is important to also combine any therapy with conventional approaches such as physiotherapy and exercise. We are happy to coordinate our treatments with your primary care physician or orthopedist at your location. In addition, we will be happy to advise you on nutritional supplements or infusion therapies that could support your treatment. Various substances are said to have an anti-inflammatory or regenerative supporting function.

Physiotherapy, Manual Therapy, Osteopathy, Insoles

Orthopedic treatment should always be given for osteoarthritis. Have a check to see if your legs are actually the same length or if you have hip misalignments that create a one-sided or incorrect body structure. In many cases, such as knee or hip osteoarthritis, muscles can stabilize the affected joint. Seek advice from a physical therapist. They can often show you specific stabilizing exercises that, if done regularly, can improve your range of motion. Use osteopathy or manual therapy to relieve any tightness or tension that may be present. Often such misalignments lead to further stress on joints.

Sports and Physical Activity

In many cases, moderate exercise has very positive influences on the course of osteoarthritis. Regular cycling is very promising for knee osteoarthritis. However, have your saddle height adjusted in advance at a bicycle store so that no incorrect positioning occurs. Swimming is also a very low-impact sport. You should mainly do crawl, backstroke or breaststroke with a floater. Here, one takes care to move the legs only up and down, as one would do in crawl swimming. Walking or Nordic walking can also have a very positive effect. However, in all cases, discuss your sport with your physiotherapist. In more advanced stages, water gymnastics may be the sport of choice.

Nutritional Supplementation and Nutrition

There are still few proven correlations here, but there are some promising approaches. A change in diet to a diet low in meat and rich in vegetables can help. Alcohol and nicotine should be avoided as they damage cartilage cells. Anti-inflammatory supplements are often discussed. These include omega-3 fatty acids, curcumin (turmeric), chondroitin sulfate, MSM, green-lipped mussel extract, hyaluronic acids, etc. for osteoarthritis.

You can also find more information on therapy approaches for osteoarthritis in our brochure.

The first non-binding step towards your treatment - we will be happy to advise you
+49 (0) 69 50 50 00 944

Frequently Asked Questions:
Stem Cell-based Treatments for Knee Injuries and Degeneration

What is the Meniscus?

The meniscus is a piece of cartilage in the knee that acts as a shock absorber or cushion and helps to stabilize the joint. It also shields the bone end that meet in the joint from wear and tear.

What Induces a Meniscus Tear?

In many cases, all it takes to tear or damage the msnicus is a strong twist of the knee, mostly due to fast turns with blocked feet. In addition to the tear, in some cases, a piece of the torn meniscus cartilage breaks loose and moves to the knee joint, causing it to block. Like most knee injuries and damage, a meniscus tear is usually painful and debilitating.

What are Knee Ligaments?

The knee is a highly complex joint that has to withstand movements and force in many directions. Therefore, it needs special stabilizing structures and these are the tendons and ligaments. The knee has 4 ligaments:

  • Anterior cruciate ligament (ACL): in the central part of the knee and controls knee rotation and the forward-directed movement of the shin bone (tibia)
  • Posterior cruciate ligament (PCL): in the back part of the knee and controls the backwards-directed movement of the shin bone (tibia)
  • Medial collateral ligament (MCL): in the central part of the outer knee, stabilizes the inner knee
  • Lateral collateral ligament (LCL): in the central part of the inner knee, stabilizes the outer knee
ANOVA-IRM-Germany-stem-cell-therapy-knee-joint-tendons-ligaments-meniscus-damage | ANOVA IRM

Human knee architecture with ligaments
ANOVA IRM - Germany

Early Detection of Joint Changes can Prevent Osteoarthritis

While the concept of prevention through early detection of benign precancerous lesions, e.g. colon polyps or "carcinoma in situ" of the breast, has long been established in the case of cancer, such prevention concepts do not yet exist in the case of osteoarthritis. In expert circles, however, the concept of "pre-arthrosis" has recently been the subject of scientific discussion. With the aid of modern imaging techniques, it is possible to visualize early onset structural changes in articular cartilage and subchondral bone structure that indicate the onset of osteoarthritis. Magnetic resonance imaging (MRI) and optical coherence tomography (OCT) play an important role here, although OCT requires instruments to be inserted into the joint. Caught early, countermeasures can be taken: Relieving joint stress, improving biomechanics, exercise, hormone replacement, and therapies with cytokines and stem cells can slow down osteoarthritis.

How Does Cortisone Work?

Injection of cortisone (corticosteroids) into inflamed joints is still widely used today. It typically results in rapid pain relief, but its effects usually do not last longer than 4 weeks. However, in the long run, cortisone injections accelerate joint wear by damaging cartilage cells, which are essential for maintaining articular cartilage.


All these abbreviations stand for anti-inflammatory drug groups that are used for inflammatory processes and diseases such as rheumatism, osteoarthritis and arthritis. NS always stands for non-steroidal, i.e. substances that are not derived from steroids such as cortisone. All non-steroidal anti-inflammatory drugs have sometimes serious side effects such as damage to the gastrointestinal mucosa or heart and kidney damage. Some preparations have therefore been withdrawn from the market.

  • NSAID - non-steroidal anti-inflammatory drug
  • NSAP - non-steroidal anti-inflammatory drug
  • NSAID - non-steroidal anti-inflammatory drug (translated non-steroidal anti-inflammatory drug)

What are Anti-Phlogistic Drugs?

Anti-phlogistic drugs are anti-inflammatory drugs. Anti-inflammatory drugs include the following groups of drugs:

  • Glucocorticoids (e.g., cortisone).
  • Non-steroidal anti-inflammatory drugs (NSAIDs, non-steroidal anti-rheumatic drugs)
  • Immunosuppressants (DMARDs, disease-modifying anti-rheumatic drugs
  • Certain novel biologic-derived drugs (biologicals, e.g., JAK inhibitors)

What is Bone Marrow Concentrate - BMC?

Bone Marrow concentrate (BMC) is a source for Mesenchymal Stem Cells (MSCs) and Hematopoietic Stem cells (HSC). It contains many important growth and regenerative factors, in addition to the MSC and HSC in natural composition. The BMC procedure is relatively simple and minimally invasive, therefore it has been a favorite source for stem cell-based therapies in the previous decades. Many clinics rely on BMC as their main stem cell treatment, sometimes with exaggerated claims. However, BMC has demonstrated impressive results for effective treatment of numerous diseases, among them being osteoarthritis. Read more about our BMC Treatment here.

What is Platelet Rich Plasma - PRP?

Platelet Rich Plasma (PRP) is a blood-derived, cellular product with concentrated supply of regenerative growth factors and cytokines, obtained from the patient's own blood. It is very simple to acquire, and it has shown promising results in the treatment of several inflammatory and degenerative diseases. For the treatment of specific diseases, it can be combined with BMC or adMSCs, as it has synergistic additive effects to the treatment. PRP has "special" functions: it serves as a growth medium to maintain stem cells healthy; ensures adequate cellular environment where enough energy is provided to allow the cells to perform their regenerative work.

Is Therapeutic Success Guaranteed?

No therapy can guarantee a 100% success after treatment. However, in the case of experimental therapies such as stem cell therapy, the attending physician must perform a benefit-to-risk analysis for each patient and determine both the benefits and the risks for that particular patient. If the potential benefit outweighs the potential side effects, the doctor may recommend experimental therapy.

The first non-binding step towards your treatment - we will be happy to advise you
+49 (0) 69 50 50 00 944

References and Literature - Stem Cell-based Therapies and Knee Injuries and Degeneration

  1. Kahn, Timothy L., and Ran Schwarzkopf. "Do Total Knee Arthroplasty Patients Have a Higher Activity Level Compared to Patients With Osteoarthritis?." Geriatric Orthopaedic Surgery & Rehabilitation 7.3 (2016): 142-147.
  2. Skou, Søren T., et al. "A randomized, controlled trial of total knee replacement." New England Journal of Medicine 373.17 (2015): 1597-1606.
  3. Metsna, Vahur, Sigrid Vorobjov, and Aare Märtson. "Prevalence of anterior knee pain among patients following total knee arthroplasty with nonreplaced patella: a retrospective study of 1778 knees." Medicina 50.2 (2014): 82-86.
  4. Riddle, Daniel L., William A. Jiranek, and Curtis W. Hayes. "Use of a validated algorithm to judge the appropriateness of total knee arthroplasty in the United States: a multicenter longitudinal cohort study." Arthritis & Rheumatology 66.8 (2014): 2134-2143.
  5. Wylde, Vikki, et al. "Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants." PAIN® 152.3 (2011): 566-572.
  6. Fuzier, Régis, et al. "Analgesic drug consumption increases after knee arthroplasty: a pharmacoepidemiological study investigating postoperative pain." PAIN® 155.7 (2014): 1339-1345. International Osteoporosis Foundation
  7. Lalmohamed, Arief, et al. "Changes in mortality patterns following total hip or knee arthroplasty over the past two decades: a nationwide cohort study." Arthritis & Rheumatology 66.2 (2014): 311-318.
  8. Lalmohamed, Arief, et al. "Timing of acute myocardial infarction in patients undergoing total hip or knee replacement: a nationwide cohort study." Archives of internal medicine 172.16 (2012): 1229-1235.
  9. Singh, Jasvinder A., et al. "Smoking as a risk factor for short‐term outcomes following primary total hip and total knee replacement in veterans." Arthritis care & research 63.10 (2011): 1365-1374.
  10. Houdek MT. Mesenchymal stem cell therapy for osteoarthritis : current perspectives. 2015:117-124.
  11. Tang J, Cui W, Song F, Zhai C. Effects of mesenchymal stem cells on interleukin-1 β -treated chondrocytes and cartilage in a rat osteoarthritic model. 2015:1753-1760. doi:10.3892/mmr.2015.3645.
  12. Mazor M, Lespessailles E, Coursier R. Mesenchymal stem-cell potential in cartilage repair : an update Osteoarthritis. 2014;18(12):2340-2350. doi:10.1111/jcmm.12378.
  13. Song F, Tang J, Geng R, et al. Comparison of the efficacy of bone marrow mononuclear cells and bone mesenchymal stem cells in the treatment of osteoarthritis in a sheep model. 2014;7(4):1415-1426.
  14. Ham O, Lee CY, Kim R, et al. Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis. 2015;(April):14961-14978. doi:10.3390/ijms160714961.
  15. Kristjánsson B, Honsawek S. Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis. 2014;2014. doi:10.1155/2014/194318.
  16. Centeno, Christopher, et al. "Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft." BioMed research international 2014 (2014).
  17. Toh WS, Foldager CB, Pei M. Advances in Mesenchymal Stem Cell-based Strategies for Cartilage Repair and Regeneration. Stem Cell Rev Rep. 2014;10:686-696. doi:10.1007/s12015-014-9526-z.
  18. Centeno, Christopher J., et al. "Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells, platelet lysate and dexamethasone." Annals of Transplantation 9 (2008): 246-251.
  19. Orozco, Lluis, et al. "Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results." Transplantation 97.11 (2014): e66-e68.
  20. Filardo, Giuseppe, et al. "Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics." Knee surgery, sports traumatology, arthroscopy 21.8 (2013): 1717-1729.
  21. Jo, Chris Hyunchul, et al. "Intra‐articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof‐of‐concept clinical trial." Stem cells 32.5 (2014): 1254-1266.
  22. Vangsness, C. Thomas, et al. "Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy." J Bone Joint Surg Am 96.2 (2014): 90-98.

  1. Georg Hansmann, Philippe Chouvarine, Franziska Diekmann, Martin Giera, Markus Ralser, Michael Mülleder, Constantin von Kaisenberg, Harald Bertram, Ekaterina Legchenko & Ralf Hass "Human umbilical cord mesenchymal stem cell-derived treatment of severe pulmonary arterial hypertension". Nature Cardiovascular Research volume 1, pages568–576 (2022).
  2. Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis . Arthritis Rheum. 2003;48:3464–74.
  3. Lee KB, Hui JH, Song IC, Ardany L, et al. Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cell. 2007;25:2964–71.
  4. Saw KY, Hussin P, Loke SC, et al. Articular cartilage regeneration with autologous marrow aspirate and hyaluronic acid: an experimental study in a goat model. Arthroscopy . 2009;25(12):1391–400.
  5. Black L, Gaynor J, Adams C, et al. Effect of intra-articular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Vet Ther. 2008;9:192-200.
  6. Centeno C, Busse D, Kisiday J, et al. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008;11(3):343–53.
  7. Centeno C, Kisiday J, Freeman M, et al. Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: a case study. Pain Physician. 2006;9:253–6.
  8. Centeno C, Schultz J, Cheever M. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell. 2011;5(1):81–93.
  9. Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose derived stem cells: a case series. J Med Case Rep. 2001;5:296.
  10. Kuroda R, Ishida K, et al. Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells. Osteoarthritis Cartilage. 2007;15:226–31.
  11. Emadedin M, Aghdami N, Taghiyar L, et al. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012;15(7):422–8.
  12. Saw KY et al. Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial. Arthroscopy. 2013;29(4):684–94.
  13. Vangsness CT, Farr J, Boyd J, et al. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy. J Bone Joint Surg. 2014;96(2):90–8.
  14. Freitag, Julien, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy–a review. BMC musculoskeletal disorders 17.1 (2016): 230.
  15. Maumus, Marie, Christian Jorgensen, and Danièle Noël. " Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. " Biochimie 95.12 (2013): 2229-2234.
  16. Dostert, Gabriel, et al. " How do mesenchymal stem cells influence or are influenced by microenvironment through extracellular vesicles communication?. " Frontiers in Cell and Developmental Biology 5 (2017).
  17. Chaparro, Orlando, and Itali Linero. " Regenerative Medicine: A New Paradigm in Bone Regeneration. " (2016).
  18. Toh, Wei Seong, et al. " MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. " Seminars in Cell & Developmental Biology. Academic Press, 2016.
  19. Chaparro, Orlando, and Itali Linero. " Regenerative Medicine: A New Paradigm in Bone Regeneration. " (2016).
  20. S. Koelling, J. Kruegel, M. Irmer, J.R. Path, B. Sadowski, X. Miro, et al., Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis , Cell Stem Cell 4 (2009) 324–335.
  21. B.A. Jones, M. Pei, Synovium-Derived stem cells: a tissue-Specific stem cell for cartilage engineering and regeneration , Tissue Eng. B: Rev. 18 (2012) 301–311.
  22. W. Ando, J.J. Kutcher, R. Krawetz, A. Sen, N. Nakamura, C.B. Frank, et al., Clonal analysis of synovial fluid stem cells to characterize and identify stable mesenchymal stromal cell/mesenchymal progenitor cell phenotypes in a porcine model: a cell source with enhanced commitment to the chondrogenic lineage, Cytotherapy 16 (2014) 776–788.
  23. K.B.L. Lee, J.H.P. Hui, I.C. Song, L. Ardany, E.H. Lee, Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model, Stem Cells 25 (2007) 2964–2971.
  24. W.-L. Fu, C.-Y. Zhou, J.-K. Yu, A new source of mesenchymal stem cells for articular cartilage repair: mSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model , Am. J. Sports Med. 42 (2014) 592–601.
  25. X. Xie, Y. Wang, C. Zhao, S. Guo, S. Liu, W. Jia, et al., Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration , Biomaterials 33 (2012) 7008–7018.
  26. E.-R. Chiang, H.-L. Ma, J.-P. Wang, C.-L. Liu, T.-H. Chen, S.-C. Hung, Allogeneic mesenchymal stem cells in combination with hyaluronic acid for the treatment of osteoarthritis in rabbits , PLoS One 11 (2016) e0149835.
  27. H. Nejadnik, J.H. Hui, E.P. Feng Choong, B.-C. Tai, E.H. Lee, Autologous bone marrow–derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study , Am. J. Sports Med. 38 (2010) 1110–1116.
  28. I. Sekiya, T. Muneta, M. Horie, H. Koga, Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects , Clin. Orthop. Rel. Res. 473 (2015) 2316–2326.
  29. Y.S. Kim, Y.J. Choi, Y.G. Koh, Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes , Am. J. Sports Med. 43 (2015) 2293–2301.
  30. W.-L. Fu, Y.-F. Ao, X.-Y. Ke, Z.-Z. Zheng, X. Gong, D. Jiang, et al., Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment , Knee 21 (2014) 609–612.
  31. Y.-G. Koh, O.-R. Kwon, Y.-S. Kim, Y.-J. Choi, D.-H. Tak, Adipose-derived mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial , Arthrosc. J. Arthrosc. Relat. Surg. 32 (2016) 97–109.
  32. T.S. de Windt, L.A. Vonk, I.C.M. Slaper-Cortenbach, M.P.H. van den Broek, R. Nizak, M.H.P. van Rijen, et al., Allogeneic mesenchymal stem cells stimulate cartilage regeneration and are safe for single-Stage cartilage repair in humans upon mixture with recycled autologous chondrons , Stem Cells (2016) (n/a-n/a).
  33. L. da Silva Meirelles, A.M. Fontes, D.T. Covas, A.I. Caplan, Mechanisms involved in the therapeutic properties of mesenchymal stem cells , Cytokine Growth Factor Rev. 20 (2009) 419–427.
  34. W.S. Toh, C.B. Foldager, M. Pei, J.H.P. Hui, Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration , Stem Cell Rev. Rep. 10 (2014) 686–696.
  35. R.C. Lai, F. Arslan, M.M. Lee, N.S.K. Sze, A. Choo, T.S. Chen, et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury , Stem Cell Res. 4 (2010) 214–222.
  36. S. Zhang, W.C. Chu, R.C. Lai, S.K. Lim, J.H.P. Hui, W.S. Toh, Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration, Osteoarthr . Cartil. 24 (2016) 2135–2140.
  37. S. Zhang, W. Chu, R. Lai, J. Hui, E. Lee, S. Lim, et al., 21 – human mesenchymal stem cell-derived exosomes promote orderly cartilage regeneration in an immunocompetent rat osteochondral defect model , Cytotherapy 18 (2016) S13.
  38. C.T. Lim, X. Ren, M.H. Afizah, S. Tarigan-Panjaitan, Z. Yang, Y. Wu, et al., Repair of osteochondral defects with rehydrated freeze-dried oligo[poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model
  39. A. Gobbi, G. Karnatzikos, S.R. Sankineani, One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee , Am. J. Sports Med. 42 (2014) 648–657.
  40. A. Gobbi, C. Scotti, G. Karnatzikos, A. Mudhigere, M. Castro, G.M. Peretti, One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years , Knee Surg. Sports Traumatol. Arthrosc. (2016) 1–8.
  41. A. Gobbi, G. Karnatzikos, C. Scotti, V. Mahajan, L. Mazzucco, B. Grigolo, 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 2 (2011) 286–299.
  42. K.L. Wong, K.B.L. Lee, B.C. Tai, P. Law, E.H. Lee, J.H.P. Hui, Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up , Arthrosc. J. Arthrosc. Relat. Surg. 29 (2013) 2020–2028.
  43. J.M. Hare, J.E. Fishman, G. Gerstenblith, et al., Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the poseidon randomized trial, JAMA 308 (2012) 2369–2379.
  44. L. Wu, J.C.H. Leijten, N. Georgi, J.N. Post, C.A. van Blitterswijk, M. Karperien, Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation , Tissue Eng. A 17 (2011) 1425–1436.
  45. L. Wu, H.-J. Prins, M.N. Helder, C.A. van Blitterswijk, M. Karperien, Trophic effects of mesenchymal stem cells in chondrocyte Co-Cultures are independent of culture conditions and cell sources , Tissue Eng. A 18 (2012) 1542–1551.
  46. S.K. Sze, D.P.V. de Kleijn, R.C. Lai, E. Khia Way Tan, H. Zhao, K.S. Yeo, et al., Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells , Mol. Cell. Proteomics 6 (2007) 1680–1689.
  47. M.B. Murphy, K. Moncivais, A.I. Caplan, Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine , Exp. Mol. Med. 45 (2013) e54.
  48. M.J. Lee, J. Kim, M.Y. Kim, Y.-S. Bae, S.H. Ryu, T.G. Lee, et al., Proteomic analysis of tumor necrosis factor--induced secretome of human adipose tissue-derived mesenchymal stem cells , J. Proteome Res. 9 (2010) 1754–1762.
  49. S. Bruno, C. Grange, M.C. Deregibus, R.A. Calogero, S. Saviozzi, F. Collino, et al., Mesenchymal stem cell-derived microvesicles protect against acute tubular injury, J. Am. Soc. Nephrol. 20 (2009) 1053–1067.
  50. M. Yá˜nez-Mó, P.R.-M. Siljander, Z. Andreu, A.B. Zavec, F.E. Borràs, E.I. Buzas, et al. Biological properties of extracellular vesicles and their physiological functions (2015).
  51. C. Lawson, J.M. Vicencio, D.M. Yellon, S.M. Davidson, Microvesicles and exosomes: new players in metabolic and cardiovascular disease , J. Endocrinol. 228 (2016) R57–R71.
  52. A.G. Thompson, E. Gray, S.M. Heman-Ackah, I. Mager, K. Talbot, S.E. Andaloussi, et al., Extracellular vesicles in neurodegenerative diseas—pathogenesis to biomarkers, Nat. Rev. Neurol. 12 (2016) 346–357.
  53. I.E.M. Bank, L. Timmers, C.M. Gijsberts, Y.-N. Zhang, A. Mosterd, J.-W. Wang, et al., The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease , Expert Rev. Mol. Diagn. 15 (2015) 1577–1588.
  54. T. Kato, S. Miyaki, H. Ishitobi, Y. Nakamura, T. Nakasa, M.K. Lotz, et al., Exosomes from IL-1 stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes , Arthritis. Res. Ther. 16 (2014) 1–11.
  55. R.W.Y. Yeo, S.K. Lim, Exosomes and their therapeutic applications, in: C. Gunther, A. Hauser, R. Huss (Eds.), Advances in Pharmaceutical Cell TherapyPrinciples of Cell-Based Biopharmaceuticals, World Scientific, Singapore, 2015, pp. 477–491.
  56. X. Qi, J. Zhang, H. Yuan, Z. Xu, Q. Li, X. Niu, et al., Exosomes secreted by human-Induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats , Int. J. Biol. Sci. 12 (2016) 836–849.
  57. R.C. Lai, F. Arslan, S.S. Tan, B. Tan, A. Choo, M.M. Lee, et al., Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles , J. Mol. Cell. Cardiol. 48 (2010) 1215–1224.
  58. Y. Zhou, H. Xu, W. Xu, B. Wang, H. Wu, Y. Tao, et al., Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro , Stem Cell Res. Ther. 4 (2013) 1–13.
  59. Y. Qin, L. Wang, Z. Gao, G. Chen, C. Zhang, Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo , Sci. Rep. 6 (2016) 21961.
  60. M. Nakano, K. Nagaishi, N. Konari, Y. Saito, T. Chikenji, Y. Mizue, et al., Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes , Sci. Rep. 6 (2016) 24805.
  61. K. Nagaishi, Y. Mizue, T. Chikenji, M. Otani, M. Nakano, N. Konari, et al., Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes , Sci. Rep. 6 (2016) 34842.
  62. S.R. Baglio, K. Rooijers, D. Koppers-Lalic, F.J. Verweij, M. Pérez Lanzón, N. Zini, et al., Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species , Stem Cell Res. Ther. 6 (2015) 1–20.
  63. T. Chen, R. Yeo, F. Arslan, Y. Yin, S. Tan, Efficiency of exosome production correlates inversely with the developmental maturity of MSC donor, J. Stem Cell Res. Ther. 3 (2013) 2.
  64. R.C. Lai, S.S. Tan, B.J. Teh, S.K. Sze, F. Arslan, D.P. de Kleijn, et al., Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome , Int. J. Proteomics 2012 (2012) 971907.
  65. T.S. Chen, R.C. Lai, M.M. Lee, A.B.H. Choo, C.N. Lee, S.K. Lim, Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs , Nucleic Acids Res. 38 (2010) 215–224.
  66. R.W. Yeo, R.C. Lai, K.H. Tan, S.K. Lim, Exosome: a novel and safer therapeutic refinement of mesenchymal stem cell, J. Circ. Biomark. 1 (2013) 7.
  67. R.C. Lai, R.W. Yeo, S.K. Lim, Mesenchymal stem cell exosomes, Semin. Cell Dev. Biol. 40 (2015) 82–88.
  68. B. Zhang, R.W. Yeo, K.H. Tan, S.K. Lim, Focus on extracellular vesicles: therapeutic potential of stem cell-derived extracellular vesicles , Int. J. Mol. Sci. 17 (2016) 174.
  69. Hu G-w, Q. Li, X. Niu, B. Hu, J. Liu, Zhou S-m, et al., Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice , Stem Cell Res. Ther. 6 (2015) 1–15.
  70. J. Zhang, J. Guan, X. Niu, G. Hu, S. Guo, Q. Li, et al., Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis , J. Transl. Med. 13 (2015) 1–14.
  71. B. Zhang, M. Wang, A. Gong, X. Zhang, X. Wu, Y. Zhu, et al., HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing, Stem Cells 33 (2015) 2158–2168.
  72. B. Zhang, Y. Yin, R.C. Lai, S.S. Tan, A.B.H. Choo, S.K. Lim, Mesenchymal stem cells secrete immunologically active exosomes , Stem Cells Dev. 23 (2013) 1233–1244.
  73. C.Y. Tan, R.C. Lai, W. Wong, Y.Y. Dan, S.-K. Lim, H.K. Ho, Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models , Stem Cell Res. Ther. 5 (2014) 1–14.
  74. C. Lee, S.A. Mitsialis, M. Aslam, S.H. Vitali, E. Vergadi, G. Konstantinou, et al., Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension , Circulation 126 (2012) 2601–2611.
  75. B. Yu, H. Shao, C. Su, Y. Jiang, X. Chen, L. Bai, et al., Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1 , Sci. Rep. 6 (2016) 34562.
  76. Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof of concept clinical trial. Stem Cells. 2014;32(5):1254–66.
  77. Vega, Aurelio, et al. Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation. 2015;99(8):1681–90.
  78. Davatchi F, Sadeghi-Abdollahi B, Mohyeddin M, et al. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011;14(2):211–5
  79. Hernigou P, Flouzat Lachaniette CH, Delambre J, et al. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case- controlled study. Int Orthop. 2014;38(9):1811–1818
  80. Galli D, Vitale M, Vaccarezza M. Bone marrow-derived mesenchymal cell differentiation toward myogenic lineages: facts and perspectives. Biomed Res Int. 2014;2014:6.
  81. Beitzel K, Solovyova O, Cote MP, et al. The future role of mesenchymal Stem cells in The management of shoulder disorders . Arthroscopy. 2013;29(10):1702–1711.
  82. Isaac C, Gharaibeh B, Witt M, Wright VJ, Huard J. Biologic approaches to enhance rotator cuff healing after injury. J Shoulder Elbow Surg. 2012;21(2):181–190.
  83. Malda, Jos, et al. " Extracellular vesicles [mdash] new tool for joint repair and regeneration. " Nature Reviews Rheumatology (2016).

  1. Xu, Ming, et al. " Transplanted senescent cells induce an osteoarthritis-like condition in mice. " The Journals of Gerontology Series A: Biological Sciences and Medical Sciences (2016): glw154.
  2. McCulloch, Kendal, Gary J. Litherland, and Taranjit Singh Rai. " Cellular senescence in osteoarthritis pathology ." Aging Cell (2017).

Patient Services at ANOVA Institute for Regenerative Medicine

  • Located in the center of Germany, quick access by car or train from anywhere in Europe
  • Simple access worldwide, less than 20 minutes from Frankfurt Airport
  • Individualized therapy with state-of-the-art stem cell products
  • Individually planned diagnostic work-up which include world-class MRI and CT scans
  • German high quality standard on safety and quality assurance
  • Personal service with friendly, dedicated Patient Care Managers
  • Scientific collaborations with academic institutions to assure you the latest regenerative medical programs