Stem Cell Therapy - What is Regenerative Medicine?

Regenerative Medicine is a new field of medicine with one goal in mind: to heal and restore normal function of damaged tissues and organs. Just like the human body itself, regenerative medicine utilizes stem cells to replace damaged cells and tissues. Stem cells are, therefore, considered to be one of the most powerful tools in treating diseases. They go beyond conventional methods to repair and regenerate disease-related damage, by returning tissues and organs to a healthier state.

Stem Cell Therapy - an Experimental Therapy

Stem cell therapy is an experimental form of therapy. Most stem cell therapies worldwide are currently not approved, as the approval process for a new form of therapy is typically a lengthy process and, in the case of stem cells, this has not yet been completed. Therefore, the legal use is restricted to medical clinics with legal permissions. ANOVA has all necessary legal permission for its products since 2018 and is authority controlled ensuring safe products.

The typical course of drug development involves a multi-stage clinical trial that begins with scientific research in the laboratory, continues with preclinical studies (studies on animals) and ends with phase I to III clinical studies in humans. Most stem cell-based therapies, like the ones we offer, have so far not undergone any or no full clinical testing. The effectiveness of such a therapy is currently still pending. In the context of experimental therapy, a doctor with a special license is still able to use novel therapies, as long as they have been classified as safe and the benefits of the therapy can be shown to outweigh the potential risks.

Stem Cell Therapies at ANOVA IRM Germany

Bone Marrow Concentrate (BMC) and Mesenchymal Stem Cells (MSCs) are the most abundant form of autologous adult stem cells and are thus well suited for clinical use. They are relatively easily harvested from the bone marrow (BMCs) or from the subcutaneous ("under the skin") fat (MSCs).

Currently, whole body therapies or therapies for chronic diseases at ANOVA are based either on a cell-free MSC stem cell-based therapy, which is the Stem Cell Secretome. It is the application of the sum of the secretion products (communication molecules) of MSCs. 

For localized treatment, we offer combination therapies with BMC (bone marrow concentrate, bone marrow stem cells) and Platelet Rich Plasma (PRP), a medium that is rich in growth factors and other cytokines (molecules from the immune system) that stimulates healing. Both can additionally be supplemented with our infusion treatments as they seamlessly synergize together.

ANOVA offers individualized stem cell therapies that are best suited for the particular condition of the patient - the treatment plan is therefore personalized. The application of these therapies depends entirely on the patient’s medical condition.

Why Does ANOVA Only Offer Autologous Stem Cell Therapies?

One of the safest and most effective forms of stem cell treatment we use in our clinic utilizes autologous stem cells, which are stem cells derived from the individual patient.

By using autologous stem cells for stem cell-based therapies, there is very little to no risk of transmitting infectious diseases or adverse immune reactions. These can occur when using allogeneic stem cells (cells from foreign donors) if contamination or cross-contamination occurs during cultivation and propagation of the MSC (mesechymal stem cells).

For this reason, ANOVA offers only autologous stem cell therapies.

Learn more about stem cell therapy in Germany - contact us.




ANOVA-IRM-Deutschland-Stammzellen-Injektion-Kultivierung-Vermehrung-3-Flaschen

Cultivation of MSC

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)

How Do Stem Cells Heal?

Stem cells, as explained previously, have the power to turn into any cell type, all the way from bone cells to brain cells, heart cells, nerve cells, kidney cells, etc. This is what defines stem cells. However, the potency to differentiate into any body cell type is not what defines their healing powers, as not all stem cell types are able to transform into any cell type. Only a selected few, such as Bone Marrow Cells (BMC) and Mesenchymal Stem Cells (MSCs), have been identified to turn into most cells types and have been successfully used in medicine to treat diseases. They have been shown to hold several major therapeutic effects, such as:

  • Down-regulation of immune processes and inflammation
  • Suppression of apoptosis ("programmed cell death", i.e. the suicide of cells)
  • Activation of resident stem cells - up-regulate progenitor cell mobilization
  • Induce angiogenesis (development of new blood vessels) - leading to better blood supply
  • Promote neurogenesis (development of new nervous tissue)
  • Neuroprotection
  • Antioxidation

After initial damage to tissues or organs, such as mechanical forces in trauma or the lack of blood supply in strokes and heart attacks, further damage is caused by immune processes and inflammation. Sub-critically injured cells, which are usually found in the vicinity of the damaged tissue or organ, primarily commit suicide instead of repairing themselves. This process further increases the damaged tissue volume. To repair this damage, which is (potentially) possible in most organs by the specific stem cells residing in them, is very slow or does not happen at all without external stimulation. In such cases, stem cell therapies have been demonstrated to be extremely effective in stimulating repair and limiting further damage.

Stem Cell Therapy: Different Types of Stem Cells

Stem cells exist in many different types as they have been identified in various tissues and organs. Each type of stem cell is classified by: their origin in the body, and their potential (potency) to differentiate (transform) into other cell types. This potential varies among stem cell types.

Some stem cells are capable of differentiating themselves into any cell type of body (pluripotent). Others, on the other hand, are able to transform into many cell types (multipotent), while some are only able to differentiate themselves into few (oligopotent) or one cell type (unipotent).

Having this in mind, it is important to note that not all stem cell types are suitable for treating patients. For example, the use of Embryonic Stem Cells (ESCs) for treating patients is restricted due to ethical issues, and their potential to grow into tumors.

One of the safest ways to apply stem cell treatments, which we employ at ANOVA, is to make use of autologous stem cells, i.e. stem cells derived from the patient themselves. By using autologous stem cells for the treatment of patients, there is very minimal to no risk of tumor formation, the transmission of infectious diseases or adverse immune reactions.

ANOVA-IRM-Deutschland-Stammzellen-Injektion-Kultivierung-Vermehrung-3-Flaschen

Different types of stem cells
ANOVA IRM, Germany

ANOVA's Stem Cell Secretome Therapy:
The Next Generation of Regenerative Medicine

Early stem cell research indicated that stem cells heal by replacing damaged cells in injured organs. Now, it has become evident that the major effects of tissue repair are not entirely based on direct stem cell implantation, but rather by the secretion of soluble (paracrine) factors from the stem cells themselves.

This discovery has prompted ANOVA to explore a completely new therapeutical approach in regenerative medicine, which has ultimately lead to our novel, safe and cell-free treatment: The ANOVA's Stem Cell Secretome Therapy.

As the first clinic in Europe, ANOVA's Stem Cell Secretome therapy utilizes autologous stem cells, i.e. cells that are derived from the patient itself, to mass produce the secretory factors (that retain the regenerative powers of stem cells), At ANOVA, a minimally invasive mini-liposuction procedure is performed, which allows for the isolation of stem cells from the subcutaneous fat (adipose tissue) of the patient.

This method does not rely on direct stem cell transplantation, and it doesn't have to. Latest scientific research has shown that stem cell-free therapies, such as the Stem Cell Secretome, offer the same efficacy as traditional stem cell transplantation therapies, with higher safety and minimized risk profiles for the patient.

Frequently Asked Questions About Stem Cell Therapies - FAQ:
International Application of Different Types of Stem Cells - Overview.

Stem cells have a seemingly unfathomable potential and are being tested by companies and universities worldwide with regard to their clinical significance as a form of therapy for numerous diseases. In parallel, however, stem cells are already being legally used by physicians and clinics such as ANOVA IRM to offer patients with certain diseases a new therapeutic option. ANOVA IRM operates in Offenbach, Germany and is officially controlled. Internationally, on the other hand, there are numerous providers of stem cell therapies that may not be legal, may not have been tested, or may not have been monitored by the authorities. ANOVA IRM clearly distances itself from this. The following therapies are generally available:

Stem Cell Therapies by Donor:

  • Autologous stem cells (donor and recipient are identical), therefore safer in terms of infection risks and immune responses, more expensive as 1 donation corresponds to only 1 patient, age of stem cells (culture duration): often no or few steps, which leads to expectation of higher efficacy potential
  • Allogeneic or homologous stem cells (human, donor is a human, but not also the recipient), higher risk in terms of infection risks and immune responses, cheaper as 1 donation is used for several or many patients, age of stem cells (culture duration): often very high, which suggests a lower effective potential
  • Heterologous stem cells: The donor is an animal, the recipient is a human. These stem cells should not be injected as they carry a high risk of infection as well as a high immunological risk. Their should always be subject to special testing and regulatory monitoring.

ANOVA IRM GmbH uses only autologous stem cells and stem cells that have not been multiplied at all or have been multiplied only slightly, due to their higher safety and quality. All stem cells are harvested, processed and applied in Offenbach am Main, Germany.


Stem Cell Therapies by age of Donor:

  • Adult stem cells are derived from adult donors. This form of stem cells is most commonly used for therapies. The ANOVA IRM uses only adult stem cells. These cells have a very large and sufficient medical potential.
  • Fetal stem cells are derived from human fetuses. For ethical reasons, they should not be used for stem cell therapies, or only to an extremely limited extent. These cells are considered to have a higher differentiation potential, but this could be important for medical use only in the field of tissue engineering, as tissue production in the laboratory.
  • Embryonic stem cells: are derived from human embryos. Internationally, the use or research on embryonic cells is very limited, as this involves major ethical problems. Embryonic stem cells have the highest potential in terms of differentiation ability. However, as with fetal cells, this is not relevant or necessary for use in the field of stem cell therapies.

ANOVA IRM GmbH uses only adult autologous  stem cells due to ethical aspects and international guidelines as well as sufficient quality. All stem cells are harvested, processed and applied in Offenbach am Main, Germany.


Stem Cell Therapies by Tissue of Origin of Stem Cells:

  • Bone marrow stem cells (BMC, bone marrow concentrate), simple, fast isolation, probably the most widely used in the world, very safe if controlled by authorities, used for bone marrow transplantation and treatment of e.g. osteoarthritis, arthritis, torn ligaments, back injuries and herniated discs, etc. BMC contain the natural composition of stem cells from bone marrow, including haemopoietic stem cells (blood-forming stem cells) and about 1% MSC (mesenchymal stem cells). BMC are used immediately after quality control, i.e. they are not cultured. Since BMC are produced in a closed system, their application is considered comparatively safe. ANOVA IRM uses BMC for this treatment area. You can read more about BMC here.
  • Stem cells from body fat tissue (ADSC, adipose-derived stem cells, adipogenic stem cells, AD-MSC, adipose-derived MSC) are so-called MSC (mesenchymal stem cells) derived from the fat tissue (therefore adipogenic) of a donor. Miniliposuction is a simple and fast procedure to obtain high-quality starting material from which the MSC can be isolated and subsequently cultivated and thus multiplied. Cultures are obtained that can contain e.g. 90-98% pure MSC. The application takes place after the culture phase in an open system and therefore intensive quality control before the application, i.e. with a time interval to the collection. It may be confusing that MSC can also be obtained from umbilical cords or bone marrow (see below). The ANOVA IRM uses such fat stem cells (MSC) to produce the stem cell secretome. You can read more about the secretome here.
  • SVF (stromal vascular fraction) from adipose tissue is also obtained by liposuction from adipose tissue. This tissue fraction is thus the precursor to the AD-MSCs mentioned above. ANOVA does not use SVF because this precursor contains only a few stem cells (about 1-10% depending on the patient and isolation), these cells are very stressed after isolation in the open system, and there is no time for necessary, sufficient quality control before use. For these reasons, we generally advise against the use of SVF.
  • Stem cells from the umbilical cord (HUC-MSC, human umbilical cord stem cells) are not used in ANOVA. With few exceptions, these products are used internationally as allogeneic as foreign donor products. If you are interested in these products, please check whether the supplier has a manufacturing license and whether the products are tested according to GMP. In particular, it would be necessary to check how suitability for you as a recipient is ensured immunologically.
  • MSC from bone marrow (mesenchymal stem cells, KM-MSC, bone marrow MSC, BM-MSC, bone marrow MSC) are mostly used for research purposes only, as cells from bone marrow have to be harvested and subsequently cultured. So the basis would be BMC (see above), but this is cultivated before use. This is more costly and less productive than obtaining MSC from adipose tissue and therefore AD-MSC have prevailed over BM-MSC. ANOVA does not use BM-MSC.

  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).

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)

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