ANOVA Institute for Regenerative Medicine - Offenbach, Germany:
What Diseases do we Treat? Our Therapeutic Offer

The ANOVA IRM in Offenbach, Germany treats, among other conditions, orthopedic conditions such as  osteoarthritis, acute orthopedic problems such as knee injuries, torn tendons and ligaments, back injuries, and spinal cord injuries. Furthermore, we offer stem cell-based treatments for MS, ALS, Parkinson, other chronic and inflammatory diseases such as rheumatoid arthritis as well erectile dysfunction and anti-aging programs. Below are links to overview pages of disease-related therapy services. There you will find a description of how a treatment of e.g. arthrosis might look like and proceed.

If you want to get more detailed information about stem cell therapies, i.e. the applied stem cell therapeutics, you will find them under stem cell therapies as well as the sub-chapters on bone marrow stem cells (BMC), secretome (exosomes) and PRP (platelet-rich plasma).

Contraindications

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
  • Infectious disease (hepatitis A, B, C, HIV, syphilis, or other)
                                   
Discuss your case free-of-charge with our scientific experts
+49 (0) 69 50 50 00 944

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 in your joints. This enables us to determine individually how patients should be treated and where the stem cells should be applied.

Furthermore, in consultation with you, 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 joints 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 additionally as a supportive or preventive measure because joint problems are present in several places in the body as the secretome is aimed to centrally modulate the immune response in order to inhibit over-reactions.

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?
Do you Want a Second Medical Opinion?
Book a Counseling Appointment!

We also offer a service for a second opinion on your current medical records (MRI, CT, X-ray) and treatment advice. 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.

You are also always welcome to send us an e-mail about your case or call us during our German office hours (GMT+1). 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 treatment
ANOVA IRM - Germany

ANOVA IRM - Safety and Quality

ANOVA IRM GmbH, located in Offenbach, near Frankfurt am Main, Germany, is an officially controlled German medical company. We have permits to harvest, process and manufacture stem cell products (ATMP and tissue preparations). We manufacture all our stem cell products ourselves, control them according to GFP, GMP and the European Pharmacopoeia. This ensures in the best possible way that patients receive only safe products.

Currently, ANOVA offers BMC therapy for localized conditions, which is applied in the form of a stem cell injection. We also offer combination therapies with Platelet Rich Plasma (PRP), a medium rich in growth factors and other cytokines (molecules of the immune system) that stimulate healing, and hyaluronic acid (HA).

For chronic and decentralized conditions, ANOVA offers the cell-free stem cell secretome (exosomes), in which, as the name suggests, the secretome of the stem cells is applied. In principle, these therapies can be combined as they work seamlessly together.

ANOVA offers individualized and always autologous stem cell therapies using adult stem cells (see below) that are most appropriate for the patient's condition and the patient alone. The application of these therapies depends entirely on the patient's health condition.

Our scientific experts advice you free-of-charge
+49 (0) 69 50 50 00 944

Beware of Untested and Dangerous Stem Cell Offers

When you compare ANOVA IRM's offerings with those of other manufacturers, incorporate important points such as regulatory control, quality control, type of products, and application type.

An overview of important selection criteria can be found below.

How do I Choose Stem Cell Therapy? Questions for your Treating Clinic

Safety: Products may be Contaminated

  • Is the clinic or practice officially inspected? - Ask to see the regulatory certificate of approval or permit.
  • Does the clinic operate under GFP or GMP? - These quality management systems ensure the safety and quality of the products.
  • What quality control testing is done on the product before use and after use?
  • Are quality control tests performed in accordance with European Pharmacopoeia (Europe), 21 CFR (USA)?
  • Are contract laboratories regulatory controlled if testing is done off-site?

Allogeneic or Autologous Products:

Allogeneic products from unrelated donors are always more risky than autologous stem cells (donor and recipient are the same person).

  • Who are the foreign donors? In which country are the foreign donors obtained ?
  • How is the donor control done ? Is each donor tested individually?
  • What are the donors tested for? Standard is HIV 1+2 (PCR), HBV and HCV (antibodies and antigen) and Treponema pallidum (Syphilis)

Duration: The Shorter the Procedure, the Less Time for Quality Control

  • Will you be pre-tested as a donor ? If not, the other donors will not be tested either, cross contamination may occur.
  • What quality controls are made after collection, handling and processing ?

Animal Products: Illegal, Dangerous, Uncontrolled, Risky.

These products are strongly discouraged. Inform yourself at the authorities (national drug agency, FDA) if you are offered such products.

SVF: Stromal Vascular Fraction - SVF- not risk Minimized - Inferior Product

Compared to BMC, PRP and secretome (exosomes), this product is not recommended due to its low number of stem cells, manual (contamination prone) production and short time available for application. We do not offer this product.

Our scientific experts advice you free of charge
+49 (0) 69 50 50 00 944

Frequently Asked Questions About the Therapy Aspect - FAQ

Will Health Insurance Pay for my Stem Cell Treatment?

No, currently health insurance companies in Germany generally do not pay for experimental treatments. This includes stem cell treatments, but also intensive periodontal treatments, interventional radiological prostate cancer treatments (although these achieve significantly better results) and other new types of therapy.

How Much Does Stem Cell Treatment Cost?

Each treatment is individually tailored to the patient and can cost anywhere from several hundred to several tens of thousands of dollars. We will be happy to advise you and then provide you with a cost estimate according to your treatment plan. You can find an international overview in our blog post: What does stem cell treatment cost?

Do you Treat all Patients ?

No, we only treat patients for whom our doctors consider an indication. This means that they assume that the expected therapeutic success outweighs the risk of the minor intervention. They make this decision based on evidence, current results and the state of medical science and technology.

Contraindications - Who do we not Treat?

In several patient groups, we feel the risk outweighs the benefit or there is not enough scientific material to justify treatment. In the case of pregnant women and children, we consider the risk to be too great and therefore do not treat them. We do not treat people with mental problems, because it is questionable whether the person can fully understand the information about the medical risks of the procedures and treatment. All patients must also be able to breathe on their own, otherwise the risk of anesthesia is too high.

In the case of cancer patients, the scientific data situation is still unclear. Due to their regeneration-promoting effect, stem cells could cause increased tumor growth in cancer patients. The data situation now shows that in some biological studies stem cells promote cancer growth, in others tumor growth is inhibited. For this reason, we currently only treat patients who have been tumor-free for at least 2 years.

Which Stem Cell Therapy is Recommended?
Osteoarthritis-Arthritis-Spinal Injuries-Disc Damage-MS-ALS-Parkinson-ED

Stem cell therapies are always tailored to the patient in ANOVA and are therefore patient-specific. After an intensive evaluation of the medical history and diagnostics, we recommend a type of treatment, which can be conventional or experimental. We will also advise you on any other options you may have. In general, however, the following basic scheme can be pointed out:

  • Osteoarthritis: BMC and PRP
  • Arthritis: BMC and PRP
  • Poly-arthritis: BMC and PRP on severely affected joints, secretome (exosomes) ongoing for immune modulation
  • Back injuries: BMC and PRP
  • Knee, elbow and other localized joint problem: BMC and PRP
  • Inter-vertebral disc injuries: BMC and PRP
  • MS (multiple sclerosis): secretome (exosomes) ongoing
  • ALS (amyothrophic lateral sclerosis): secretome (exosomes) continuous
  • Parkinson's disease (PD): Secretome (exosomes) ongoing
  • Erectile dysfunction: case-dependent BMC or secretome
  • Anti-aging: secretome and BMC if joint problems have manifested already

Choosing Stem Cells to Regenerate the Body

Stem cells are the building blocks of our body, and are widely considered as one of the most important cell types we have. Mesenchymal Stem Cells (MSCs) carry massive potential in regenerative therapies. They are capable of renewing themselves and differentiating into almost all cell types of the body. MSCs are therefore a sensible source for a variety of regenerative therapies. There are many ways to isolate MSCs from the human body. One way to isolate them is from the umbilical cord or the umbilical cord's blood. However, this approach is not easily accessible.

A far more elegant and easier way to harvest MSCs is from fat (adipose) tissue or the Bone Marrow, i.e. Bone Marrow Concentrate (BMC). Both fat tissue and bone marrow are widely used sources of MSCs. Obtaining stem cells from either tissue is considered a safe practice. The most important advantage is that they make autologous (personalized) therapies safe and easily available to patients.

Which stem cells are best suited for medical use and which ones are most effective for treating patients depends on many aspects. It mainly depends on patient's specific health condition, the processing of the tissue (for harvesting stem cells), and the way in which they are administered. Recent studies have shown that MSCs obtained from fat tissue, in some applications, offer biological advantages in immuno-modulatory effects and proliferative capacities, while MSCs from BMC are more suitable in other areas.

The latest advancement in Stem Cell-based treatments is the ANOVA Stem Cell Secretome | Exosome Therapy. In contrast to earlier indications of how stem cells work, recent research has shown that the regenerative effects of stem cells are based on soluble factors (exosomes, proteins and cytokines), that the stem cells transmit to other cells. These factors together make up the secretome, as they are released by cellular secretion. The secretome has been shown to stimulate repair and rejuvenation of damaged organs and tissues in many ways. It was shown to activate the organs' own - resident - stem cells to replace damaged cells, modulate the immune system, and improve the supply of oxygen and nutrients to tissues by inducing the growth of new blood vessels - to name a few examples. ANOVA uses MSCs as a "factory" to produce these factors in high concentrations and for your individual treatment plan.

At ANOVA Institute for Regenerative Medicine, a German Stem Cell Clinic in the heart of Europe, we have specialists who carefully evaluate each patient in order to deliver the best possible individual treatment program. Our mission is to stay at the forefront of regenerative medicine and apply our knowledge to achieve the best possible results for you.

  1. Murphy JM, Fink DJ, Hunziker EB, et al. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464–74.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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).
  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-Ddried oligo
  39. [poly(ethylene glycol) fumarate] hydrogels seeded with bone marrow mesenchymal stem cells in a porcine model, Tissue Eng. A 19 (2013) 1852–1861.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. M.B. Murphy, K. Moncivais, A.I. Caplan, Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine, Exp. Mol. Med. 45 (2013) e54.
  49. 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.
  50. 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.
  51. 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).
  52. 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.
  53. 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.
  54. 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.
  55. 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.
  56. 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.
  57. 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.
  58. 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.
  59. 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.
  60. 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.
  61. 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.
  62. 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.
  63. 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.
  64. 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.
  65. 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.
  66. 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.
  67. 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.
  68. R.C. Lai, R.W. Yeo, S.K. Lim, Mesenchymal stem cell exosomes, Semin. Cell Dev. Biol. 40 (2015) 82–88.
  69. 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.
  70. 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.
  71. 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.
  72. 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.
  73. 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.
  74. 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.
  75. 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.
  76. 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.
  77. 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.
  78. 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.
  79. 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
  80. 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
  81. Galli D, Vitale M, Vaccarezza M. Bone marrow-derived mesenchymal cell differentiation toward myogenic lineages: facts and perspectives. Biomed Res Int. 2014;2014:6.
  82. 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.
  83. 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.
  84. Malda, Jos, et al. "Extracellular vesicles [mdash] new tool for joint repair and regeneration." Nature Reviews Rheumatology (2016).

  1. Rubio-Azpeitia E, Andia I. Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro experience. Muscles Ligaments Tendons J. 2014;4(1):52–62.

  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