2. Home
  3. Diseases Treated
  4. Neurodegenerative Diseases
  5. Parkinson´s Disease (PD)

Stem Cell-based Secretome - Exosome Treatment for Parkinson's Disease
at ANOVA IRM in Offenbach, Germany

Parkinson’s Disease (PD) affects millions of people worldwide. The disease is characterized by a slow and progressive deterioration of nerve cells (neurons). It is caused by the death of dopamine-producing neurons in the brain. All currently available medications for Parkinson's are limited to medicating the symptoms only.

Parkinson stem cell treatments have demonstrated the ability to stimulate repair and regenerate damaged neurons. ANOVA's Stem Cell Secretome Therapy is the latest development from current stem cell research, allowing for an emerging treatment option that with an immense potential to slow down the disease's progression at different stages.

Parkinson’s Disease
Diagnostics - Treatment - Medication - Stem Cell Therapies

On this page we inform you about PD covering an overview on important aspects of causes, treatment options, precision diagnostics as well as our stem cell-based therapies that we offer in Offenbach (near Frankfurt am Main airport), Germany.

Jump directly to the following topics:

MSC-secretome-exosome-therapy | Germany

MSC secretome - exosome - therapy
ANOVA IRM - Germany

Conventional Parkinson Disease Therapies vs. Stem Cell Therapy

Parkinson’s Disease is a chronic neurodegenerative disorder caused by selective and gradual loss of dopamine-producing neurons. These neurons are spread throughout the brain, however, the most effected region is the “substantia nigra”. The symptoms of Parkinson's Disease are mainly tremor and rigor. At later stages the illness is characterized by more severe symptoms like speech disorder, depression or even dementia. Currently, there is no cure for Parkinson’s disease.

Nevertheless, there are few hormone replacement-based therapies which tackle the symptoms only. These pharmacological treatments are effective to control the symptoms of PD to a certain degree, with side effects, but are unable to stop neural degeneration, let alone replace dead dopaminergic cells.

ANOVA-IRM-Germany-Parkinsons-disease-PD-dopaminergic-neurons-stem-cell-therapy

Degeneration of dopaminergic neurons in Parkinson's Disease
ANOVA IRM Germany, © DOI: 10.3389/fnins.2018.00080

Stem cell research has allowed ANOVA, a German Stem Cell Clinic in the heart of Europe near Frankfurt/Main airport, to offer a novel treatment with a new therapeutical approach: The ANOVA Stem Cell Secretome is a cell free and promising treatment option for PD.

Call us today, whether you wish to apply for a treatment, or simply receive more information.

Stem Cell Treatments for Early to mid Parkinson's at
ANOVA Institute for Regenerative Medicine - Offenbach, Germany
Secretome/Exosomes of MSC

Potency Hypothesis of Stem Cell Therapies

Stem cells possess the potential to communicate with the immune cells that elicit 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 loss of function.

MSEC - Mesenchymal Stem Cell Secretome - Exosomes - Autologous

As PD is a chronic, so far not curable disease, we on-goingly treat patients with early PD with MSEC (Secretome, Exosomen, EVs) of mesenchymal stem cells (MSC, AD-MSC, adipose-derived, fat-derived stem cells) which we harvest from the patients belly in a mini-liposuction (very brief and limited liposuction) under slight sedation. Worldwide, ANOVA is the first stem cell clinic to acquire legal permission form the responsible governmental authorities and therefore, offers high quality, safe and legally-controlled autologous (own) exosome-containing secretome.

The main advantage of MSEC is that in contrast to live stem cells which would loose their therapeutic potency, can be frozen without loss of exosomes. This enables us to produce 10-20 injection doses from one liposuction which can then be administered over a longer treatment period. This is especially advantageous for repeated stimulation of cell survival and regeneration in PD. What a Secretome/Exosome is and how they compare is explained on our overview page. 

MSC-secretome-exosome-therapy | Germany

MSC secretome - exosome - therapy
ANOVA IRM - Germany

Please note that this treatment is not a cure but as any stem cell treatment an experimental, potentially disease-modifying therapy. It requires regular and repeated travelling to Offenbach, Germany.

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
  • Active infectious disease (Hepatitis A, B, C, HIV, Syphilis, or other)

Therapy Workflow for Early to mid Parkinson's Disaease

The precise workflow is described in detail on the stem cell- specific pages of BMC, Secretome/Exosomes and 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 counseling 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.

Unfortunately, we only treat patients in an early to mid stage of PD and 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 counseling 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.

Secretome/Exosome-therapy:

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) in regular intervals for the application. Depending on where you live and your travelling capacity and restrictions the treatment pattern is adjusted to your needs and abilities. The shelf life of the secretome (exosomes) is 2 years. As PD is not cureable with any treatment, we recommend a double-lipo which produces 20 doses for a continuous treatment over 2 years. Thereafter, a new liposuction has to be performed.

How Much Does Stem Cell Treatment 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 PD will cost above ten 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.

Research up-Date:
Parkinson’s Disease Therapy with Stem Cells:
How can Stem Cells Help?

Diverse stem cell types are under scientific investigations, some of which are in clinical trials, for the safety and efficacy of stem cell-based therapies for treating Parkinson’s disease. They include:

Modern stem cell research conducted with animals, mainly rats and mice, provided encouraging results in treating PD, bringing regenerative medicine a step closer to finding the cure. Looking at the science of therapies that are based on BMC, SVF and MSCs, in more detail, showed that they were not able to exert their regenerative effects in stimulating the birth of millions of new functioning neurons, from the limited stem cell pool found in the body. Ideally, this is what one could hope for, in order to cure PD.

Nevertheless, some stem cells appear to be able to migrate into the brain and unfold their regenerative effects, which is a promising feature and can help develop an effective treatment for PD. These cells are recruited via paracrine signalling by extracellular vesicles (messaging products) that stem cells secrete in order to communicate with their surroundings. Consequently, the production and release of neuro-trophic (stimulating growth of nervous tissue) factors is what ultimately induces these regenerative effects. The so-called Stem Cell Secretome mainly consists of the sum of these released factors (exosomes, micro-vesicles, growth factors, etc.) that possess the regenerative powers of stem cells.

Stem Cell Research for Parkinson’s Disease:
What can we do Today?

The ANOVA Stem Cell Secretome Therapy for Parkinson’s disease uses Mesenchymal Stem Cells (MSCs). Clinical trials which employ MSCs to treat PD patients have so far shown encouraging results.

MSCs have been shown to secrete many trophic (e.g. prostaglandin E2, TGF-β1, HGF, SDF-1α, indoleamine-2,3-dioxygenase, IL-4, IL-6 and IL-10, SCF, LIF, FGF-2, VEGF, IL-6, EGF, VEGF, Neurotrophin-3 (NT3), SDF-1α, and BDNF) and neuro-protective factors (e.g. NGF, GDNF and BDNF).

The microRNAs (miR-29a, miR-9, miR-124, miR-145) secreted from MSCs' exosomes were also found to promote the differentiation of stem cells into neural cells. In addition to this broad spectrum of neuro-trophic and repair inducing factors, exposure of neurons and astrocytes to MSC extracted exosomes leads to an increase of miR-133b. This process promotes the functional recovery of neurons in PD and Spinal Cord Injury.

ANOVA's Stem Cell Secretome is an uniquely designed method, produced specifically to harness and highly concentrate the essence of these bio-active factors, for your personalized treatment. The Secretome, likewise, is produced in full accordance with state of the art methods and German quality controls to ensure the highest product quality and safety for our patients.

We are convinced by scientific data that our method is a promising, effective and much safer treatment than direct injection of MSCs. One of the most important factors of why our method is safe is due to the fact that it relies on growing autologous (from the same patient) fat-derived mesenchymal stem cells (MSC) in a sterile laboratory setting.

New therapeutic approaches that are not solely based on symptomatic reduction, such as the increase of the autophagy process by kinase inhibitors (that are currently undergoing clinical trials) are also considered at ANOVA. They can be included when we design the treatment plan of each individual patient.

If you have any questions, with regards to our stem cell-based treatments and Parkinson's disease or the cost of treatment, then please feel free to contact us.

Frequently Asked Questions for Stem Cell Treatment of Parkinson's Disease

Are Stem Cells a Cure for Parkinson’s Disease?

Currently not. However, stem cells already hold a great potential for treating most neurodegenerative diseases, especially Parkinson’s Disease, to slow down or prevent the progression of the disease. This makes it worthwhile for patients and medical professionals alike to consider stem cell-based therapies for specific cases. Each case must be evaluated individually to ensure that the benefits outweigh the risks. In general, it can be said that for cell-based therapeutics which act on a transmitter and paracrine (inter-cell communication) level, the individual success is currently not possible to be predicted. We therefore recommend that you contact us to get an expert opinion on your case and the possibilities we can offer.

Which Stages of Parkinson's Disease can be Treated with Stem Cells?

The treatment of Parkinson’s Disease with any stem cell method is independent of the stage. Stem cells secrete many healing factors, which can potentially induce a “flourishing” effect on local resident (stem) cells, as well as anti-inflammatory effects wherever they are deployed. This has very positive effects on PD at all stages. However, anticipated results may vary are depending on the progression the treatment plan and the side medications. Contact us for a consultation.

Why is not Every Parkinson's Patient Getting Stem Cell Treatments if They are so Promising and Safe?

Novel treatments are generally not widely accepted, taught or even mentioned in medical text books or medical training events. The odds are that most doctors never heard of such treatments until sufficient clinical and scientific evidence has been accumulated in form of clinical trials. This process, while necessary, is associated with very high costs, which is why not all clinics can undergo the necessary clinical trials. We at ANOVA are invested in following the scientific progress, especially regarding its safety and efficacy, to offer this treatment option to our patients.

Is There any Guarantee That a Stem Cell-based Therapy for my Parkinson's Will Work?

There is no therapy, be it an experimental or established treatment, for which your treating physician can promise or even guarantee a therapeutic success. In the case of innovative and experimental therapies such as stem cell therapy, doctors must perform a benefit-to-risk-analysis for each individual case and ensure that the therapy is beneficial to the patient and these benefits outweigh the risks. Only when this is the case, your doctor will suggest treatment with stem cells.

What Causes Parkinson’s Disease?

The underlying cause for the death of nerve cells in the brain are unknown. Several factors are known to play a role:

  • Genes: Specific gene mutations were shown to increase the risk for PD
  • Environment: Exposure to certain toxins may increase PD risk.
  • Age: Usually the age of 60 is the age where PD is most prone to happen
  • Sex: Men are more likely to develop PD
    Occurring changes in PD

changes may be related to Lewy bodies and the alpha-synuclein (SNCA) that is contained within these Lewy bodies

What Are the Early Signs of Parkinson’s Disease?

Early symptoms and possible warning signs of Parkinson’s disease (PD) are:
• Writing becomes difficult and font is getting involuntarily smaller
• One sided tremor or shaking
• Involuntarily index finger and thumb rolling
• Dizziness or fainting
• Change of facial expression known as mask face
• Soft or lower voice then usual
• Sleep problems usually accompanied with sudden movements
• Walking and otherwise subconscious movements only seem possible when actively imitating them
• Hunching over or stooping

What are the Symptoms of Parkinson’s Disease?

Early symptoms of Parkinson’s disease often go unnoticed. Often one-sided symptoms are first to give indications, as listed below. When noted, a proper diagnose by neurologist needs to be made, as all symptoms can have other causes too:

  • Writing changes towards the end of words and sentences
  • Balance and posture problems
  • Tremor usually starting with the hand at rest or in the thumb and forefingers rolling against each other
  • Slowed movements
  • Rigid and stiff muscles
  • Speech changes
  • Decreased ability to do unconscious movements

What are the Stages of Parkinson’s Disease?

  • Parkinson Stage 1: Only mild symptoms occur in facial expressions or slight tremor. However, the daily life is only minimally affected and only one sided.
  • Parkinson Stage 2: At this stage symptoms are getting worse and affect both sides. The tremor and waling problems are getting worse. Often this is the stage where L-Dopamine is employed.
  • Parkinson Stage 3: Loss of balance and slowed movements characterize this stage. Living independently is still possible but symptoms significantly impair daily activities.
  • Parkinson Stage 4: The Symptoms are severely limiting every activity, especially walking. Movements are still possible but may require aid. Usually living alone is not possible at this stage any more.
  • Parkinson Stage 5: The final and most debilitating stage, where stiffness in legs makes movement impossible. The person requires full time nursing and is bound to the wheelchair. Usually many non-motoric symptoms set like delusions, hallucinations and depressions.

What is the Life Expectancy with Parkinson’s Disease?

The disease itself is not fatal. However, related complications and symptoms can reduce the life expectancy. A study from the UK found that the life expectancy is between 3-5 years shorter than the average, when the onset of PD is at an age of 65 or older.

What can be Done for End-Stage Parkinson’s Disease – Are Stem Cells Still an Option?

It is potentially an option, but it depends on other health factors. The Stem Cell Secretome therapy can be a treatment option for PD and can be employed in combination with other established or new treatments. We recommend that you contact us to get an expert opinion on this subject.

References and Literature - Stem Cell-based Therapies and Parkinson's Disease

  1. Riecke J. et al. "A Meta-Analysis of Mesenchymal Stem Cells in Animal Models of Parkinson's Disease." Stem cells and development 24.18 (2015): 2082-2090.
  2. Ahmed HH. et al. "Updates in the pathophysiological mechanisms of Parkinson’s disease: Emerging role of bone marrow mesenchymal stem cells." World journal of stem cells 8.3 (2016): 106.
  3. Equbal Z. and Mukhopadhyay A. "Counting on Mesenchymal Stem Cells: A Hope for Treating Parkinson’s Disease. J Stem Cells Res." Rev & Rep 3.1 (2016): 1022.
  4. Wei X. et al. "Mesenchymal stem cells: a new trend for cell therapy." Acta Pharmacologica Sinica 34.6 (2013): 747-754.
  5. Wang S. et al. "Clinical applications of mesenchymal stem cells." Journal of hematology & oncology 5.1 (2012): 19.
  6. Gu W. et al. "Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord." Neuropathology 30.3 (2010): 205-217.
  7. Wilkins A. et al. "Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro." Stem cell research 3.1 (2009): 63-70.

  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