Stem Cell Treatment for Stroke Patients
at ANOVA IRM in Offenbach, Germany

Stroke is the world leading cause of disability, while it is the third leading cause of death after cancer and heart disease. It comes without warning and causes catastrophic damage to the brain. With the most common type being acute ischemic stroke, thrombolysis is currently the only therapeutic option. Stem Cell Therapy might be the answer to patient's hopes of recovery.

Stroke
Diagnostics - Treatment - Medication - Stem Cell Therapies

On this page we inform you about stroke 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 Stroke Therapies vs. Stem Cell Therapy

The cause of a stroke is the interruption of blood flow (ischemia) to the brain, which leads to a lack of oxygen and nutrients in the effected region of the brain, causing death of neurons and glia. The functional deficits result within minutes after the onset of stroke, with negative effects on motor, sensory or cognitive function, even loss of consciousness or death.

Recent advances in thrombolysis and in neuro-protective strategies have improved the management of acute stroke. When drugs are administered a few minutes after the injury, it is possible to restore the normal functions as long as the damage is still reversible. However, shortly after the onset of the stroke, brain cells are irreversibly damaged. When this happens, restoration of blood flow might even increase the damage. Many sub-critically damaged cells, which could potentially be saved, induce apoptosis (programmed cell death - "suicide") and are therefore also irreversibly lost.

effects of stroke | ANOVA Germany

A diseased carotid artery can not only narrow down the blood path to the brain, but also break off and block the cerebral artery completely, causing a stroke.

While conventional stroke therapies can at best limit damage to the brain, stem cell therapies work on a different level (angiogenic, neurotrophic, neuro-protective and anti-infammatory) and have shown great potential in the restoration of brain function. This results in a significant change of how stroke can be treated. Until recently, regeneration of the brain and spine (Central Nervous System - "CNS") has been considered impossible in adults.

However, injection of stem cells into the cerebrospinal fluid (the liquid surrounding the brain and spine which fills its internal spaces) in stroke patients, has significantly improved the functional recovery without serious side effects. Stroke patients who have received intravenous infusions of MSCs have experienced significant functional improvements with fewer neurological deficits and without adverse cell-related, serological or imaging defined effects.

Treatment with stem cells does not only offer a chance for a better and quicker recovery due to the effective neurological regeneration, but it also has the advantage that it can be used alongside all conventional treatment strategies; it has even been shown to synergize with them.

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 stroke.

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

Stem Cell Treatments for Stroke at
ANOVA Institute for Regenerative Medicine - Offenbach, Germany
BMC and Secretome/Exosomes

Potency Hypothesis of Stem Cell Therapies

Stem cells possess the potential to communicate with the immune cells that elicit the inflammation and by natural, so far not understood mechanisms may inhibit this immune-over-reaction. Furthermore, stem cells have the ability to stimulate regeneration of tissue thereby counteracting the loss of function. The aim of a stem cell treatment is therefore, the fast inhibition of inflammatory damage and induction of regeneration. In optimal cases this may result in faster and more complete recovery after stroke.

Two Targeted Effects: Pain Relief and Progression Improvement

A stem cell treatment can elicit two effects that build on one another. First, due to the modulation of the underlying immune reaction the stem cell injection inhibits the inflammation. As inflammation often is the main cause of ongoing damage, this may limit further loss of neurons.

Second, the effects on regeneration build on the inhibition of inflammation. The brain tissues return to a resting-phase and are now able to react to healing and regenerative stimuli. With adequate on-going stem cell therapy in combination with e.g. physiotherapy, regeneration of brain cells is stimulated. As all effects are patient- and disease stage-dependent and may be influenced by additional, external factors, we always apply individual treatment plans.

BMC - Bone Marrow Concentrate - Autologous

Autologous (self) BMC are our main therapy option for locally-restricted and mild conditions as BMC is a one bone marrow donation - one injection treatment.

In such cases we treat specifically this disc or this spinal segment with targeted, localized BMC injections. BMC contains autologous meaning patients own, adult  stem cells (hematopoietic and mesenchymal stem cells in natural composition) which we isolate and concentrate from your pelvis crest in a short process under slight sedation.
These stem cells are supposed to inhibit the inflammation thereby relieving you from pain and to stimulate regeneration of the spinal segment. For an on-going therapy, we combine BMC with PRP (platelet-rich plasma) or MSEC (see below). More information about this type of stem cell therapy is summarized on our page an BMC.

BMC-bone-marrow-concentrate-therapy | Germany

BMC - bone marrow concentrate
ANOVA IRM - Germany

MSEC - Mesenchymal Stem Cell Secretome - Exosomes - Autologous

In later stages or more wide-spread damage, we  treat stroke patients 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 regeneration after stroke. 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

Combination Treatment for Fast and Repeated Treatment

As after stroke the fast treatment is advisable to modulate inflammatory processes and a repeated treatment is recommended for on-going stimulation of regeneration, both treatment types are often combined with BMC for fast treatment and MSEC for continuous treatment over 2-3 months.

Therapy Workflow for Stroke

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, 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. Then, depending on the therapy, the tissue collection, quality control and treatment type it will take as follows:

BMC- and PRP-Therapy

Each donation and application of BMC  on-site period: 2 days (consecutive days).

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) several times for the application. The shelf life of the secretome (exosomes) is 2 years.

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 stroke can cost from a few thousand to several thousand euros. You will receive a cost estimate for all treatments in advance so that you can accurately estimate what a treatment would cost in your individual case.

Does my Health Insurance Cover the Therapy Costs?

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

Are you Interested but Uncertain?
Do you Want a Second Medical Opinion?
Book a Counselling 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

                                  
Request a second opinion on your case
+49 (0) 69 50 50 00 944

FAQ: Stem Cell Therapy for Stroke Patients

At What Time is a Stem Cell Therapy Most Efficient to Fully Recover From a Stroke?

The simple answer is, the earlier the better. However, scientists and medical professionals have not defined an endpoint for beneficial application. Beneficial effects can be experienced years after the stroke ocurred, but the mechanism of action could be entirely different. For example: applying stem cell therapies at a later time could potentially only induce neuro-trophic effects, while a sooner application could initiate the full range of benefical effects that stem cells have (anti-inflamation, apoptotic protection, immuno-modulation, neurotrophic). Scientific results are still inconclusive with regards to this question.


What Stem Cell Source Does ANOVA Recommend for Optimal Recovery Results After a Stroke, and how are They Administered?

This cannot be answered in a simple way, because many parameters play a role in treatment success. There are many medical aspects to be considered, as well as personal and financial aspects.
We offer personalized treatments only, which means that we evaluate each patient and each case individually and assess the risks and benefits of each treatment or treatment combination before we suggest a treatment plan.

For more information please contact us, and send all relevant medical information to give us a chance to discuss your case in our medical board meeting. For urgent (acute) cases of stroke, we will hold emergency meetings with reaction times of 24h or less.

How Many Applications of Stem Cells Does it Require to Reach the Optimal Outcome?

To date there the carried out clinical trials only offer insufficient data to answer this question. However, extrapolating from what is known about stem cells (so far) and their underlying biological mechanisms, frequent injections (initially 1-3 per month) for at least a year or two years, appears to be a good initial guess for an effective treatment. This can easily be adapted to the observed progress or biomarkers. Neurogenesis processes are always slow, even with stem cells.

I’m Currently Undergoing Treatment "XY" – Would the Stem Cell Therapy Interfere? Should I Stop Taking Medications?

No! Do not stop taking any medication prescribed by your physician before we are able to do a full assessment and provide clear advise on the matter. In some cases, stroke medications can interfere with the necessary liposuction and / or bone marrow harvesting step. This needs to be carefully assessed by our medical professionals beforehand. With regards to the the stem cell treatment itself, none of the stroke medications have been shown to have negative interferences, as the two work on an entirely different levels.

I Want the Treatment but I can not / don’t Want to fly to the ANOVA Institute in Frankfurt. Can I get the Cells via Postal Service?

No, this is not possible, due to regulatory reasons we offer our services in our clinic only. The harvest of Mesenchymal Stem Cells (MSCs) from fat as well as the application of Stem Cell Secretome, are performed strictly in our clinic by the same doctor.

Can you Guarantee Treatment Success?

Therapeutic success cannot be guaranteed with any type of treatment. Particularly in the case of experimental therapies such as stem cell-based therapies, the attending physician will perform a benefit-to-risk analysis for each individual patient and case and determine both the benefits and the risks. If the potential benefits outweigh the potential adverse events, the doctor may recommend experimental therapy.

Discuss your case charge-free with our scientific experts
+49 (0) 69 50 50 00 944

References and Literature - Stem Cell-based Therapies and Osteoarthritis

  1. Kasahara, Yukiko, Tomohiro Matsuyama, and Akihiko Taguchi. "Treatment of Autologous Bone Marrow Mononuclear Cells for Acute and Subacute Stroke." Cell Therapy for Brain Injury. Springer International Publishing, 2015. 37-46.
  2. Sun, Jinmei, et al. "Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice." Experimental neurology 272 (2015): 78-87.
  3. Lindvall O, Kokaia Z: Stem cells for the treatment of neurological disorders. Nature 2006, 441(7097):1094-1096.
  4. Rabinovich SS, Seledtsov VI, Banul NV, Poveshchenko OV, Senyukov VV, Astrakov SV, Samarin DM, Taraban VY: Cell therapy of brain stroke. Bull Exp Biol Med 2005, 139(1):126-128.
  5. Bang OY, Lee JS, Lee PH, Lee G: Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005, 57(6):874-882.
  6. Chen, Jieli, Poornima Venkat, and Michael Chopp. "Bone Marrow Mesenchymal Stromal Cell Transplantation: A Neurorestorative Therapy for Stroke." Cellular Therapy for Stroke and CNS Injuries. Springer International Publishing, 2015. 47-69.
  7. Anderson, Johnathon D., et al. "Mesenchymal stem cell-based therapy for ischemic stroke." Chinese Neurosurgical Journal 2.1 (2016): 36.
  8. Lee, Ji Yong, et al. "Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke." Scientific Reports 6 (2016).

  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