2. Home
  3. Overview
  4. Stem Cell Treatment for Neurodegenerative Diseases
  5. Stem Cells for Amyotrophic Lateral Sclerosis (ALS)

Stem Cell Therapy for Amyotrophic Lateral Sclerosis
at ANOVA IRM in Offenbach, Germany

Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive death of cerebral (upper) and spinal (lower) motor neurons. It is a complex disease which involves the activation of several cellular pathways in both neurons and glial cells. This results in a severe motor dysfunction muscles become atrophic due to the lack of nerve stimulation. Often, the origin of the disease is unknown. ALS is not a typical autoimmune disorder, since autoimmune and inflammatory abnormalities are not the cause of the disease, even though they influence its progression.

Stem cell-based therapies are being investigated for their potential role in future ALS treatment strategies. A study by Mazzini et al. reported that the procedure of ex vivo expansion of autologous Mesenchymal Stem Cells (MSCs) and transplantation into the spinal cord of humans was safe and well tolerated by the ALS patients studied. A more recent study, by the same group, however, confirmed that MSC transplantation into the spinal cord of ALS patients is not only safe, but might also serve as a treatment option for future cell-based clinical trials for the treatment of ALS.

Many current pre-clinical studies suggest that stem cell transplantation has the best effect when aimed towards protecting, rather than replacing or repairing the motor neurons of ALS patients. Because our Stem Cell Secretome preparations do not contain living cells, they may offer practical and safety-related advantages compared with cell transplantation. Stem Cell Secretome is the essence of stem cells, and may facilitate neuro-protection and recovery of neuro-motorial function. ANOVA offers this experimental and novel stem cell-based therapy patients with ALS. For more information, please feel free to contact us.

Amyotrophic Lateral Sclerosis
Diagnostics - Treatment - Medication - Stem Cell Therapies

On this page we inform you about ALS 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

Looking for patient outcomes and efficacy data?

We have compiled and evaluated clinical data from our treatments. Read the comprehensive report here:

View ANOVA ALS Real-World Data →

Translational Medicine for People Living with ALS
Understanding ALS

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a progressive neurodegenerative disorder affecting the nerve cells that control voluntary movement.[23] As upper and lower motor neurons gradually degenerate, muscles become weaker, leading over time to increasing difficulties with mobility, speech, swallowing and breathing.[23]

ALS affects approximately 5 people per 100,000 worldwide.[23] Around 90% of cases occur without a known family history (sporadic ALS), while approximately 10% are associated with inherited genetic variants, including mutations in genes such as SOD1, C9orf72, TARDBP and FUS.[22]

Although the exact causes of ALS remain incompletely understood, extensive research indicates that several biological processes contribute to disease progression. These include neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired protein homeostasis, disturbances in cellular energy metabolism and alterations of the gut–brain axis.[14],[17] Rather than representing a single disease mechanism, ALS is now widely regarded as a complex disorder involving multiple interacting pathways.[22]

This evolving understanding has stimulated growing international interest in therapeutic strategies that address several of these biological mechanisms simultaneously.

Current Standard Treatment

International treatment guidelines recommend multidisciplinary care combined with approved pharmacological therapies where appropriate. Comprehensive supportive care—including physiotherapy, nutritional support, respiratory care, speech and language therapy, and assistive technologies—remains an essential component of ALS management throughout the course of the disease.[23]

Riluzole has been the standard pharmacological treatment for ALS for almost three decades. Clinical studies have shown that the medication can modestly prolong survival in some patients, although the magnitude of benefit varies between individuals.[1],[2],[3] Like all medicines, riluzole may also cause adverse effects, including gastrointestinal symptoms and elevations of liver enzymes, making regular medical monitoring advisable during treatment.[1]

Edaravone has been approved in several countries for selected groups of ALS patients following clinical studies suggesting a reduction in functional decline in certain patient populations. The extent to which these findings can be generalised to the broader ALS population continues to be investigated.[21]

Another therapeutic approach combines sodium phenylbutyrate with taurursodiol (TUDCA). Early clinical studies generated encouraging results, although further confirmatory research has been considered important to better define its long-term clinical benefit.[10]

While approved therapies represent the current standard of care and should always be discussed with the treating neurologist, there remains a considerable unmet medical need in ALS. Worldwide, academic centres and specialised research institutions are therefore investigating additional approaches that may complement existing treatment strategies by targeting biological processes not addressed by currently approved medications.

Please use our contact form
for further information.
"> 

Our Therapeutic Approach at ANOVA IRM

ANOVA IRM is dedicated to the translation of emerging biomedical research into carefully designed patient care. Our work focuses on developing therapeutic concepts for patients with severe neurodegenerative diseases for whom current treatment options remain limited.

Where medically appropriate, treatment may be offered within the German legal framework of an individual therapeutic attempt ("individueller Heilversuch"). This framework allows physicians, in carefully selected individual cases, to consider treatment approaches that are not part of established standard therapy, provided that patients receive comprehensive medical information, understand the experimental nature of the intervention, and provide informed consent.

The therapeutic approaches described below are therefore not established standard treatments for ALS. Several components are currently being investigated in clinical research, while others are supported primarily by preclinical studies and translational scientific evidence. Their potential benefits and risks are discussed individually with each patient before any treatment decision is made.

To date, more than 70 individuals with ALS have been treated at our institution. This clinical experience continues to inform the ongoing development and refinement of our treatment concepts while contributing to a growing understanding of their practical application in routine clinical care.

Rather than focusing on a single biological pathway, our therapeutic strategy seeks to address several mechanisms that are believed to contribute to ALS progression, including neuroinflammation, impaired neuronal support, cellular ageing and disturbances of the gut-brain axis.

1. Mesenchymal Stromal Cell Secretome

One area of our work involves the therapeutic use of the mesenchymal stromal cell (MSC) secretome. Rather than transplanting living cells, this approach utilises the broad spectrum of biologically active molecules naturally released by MSCs, including growth factors, cytokines, extracellular vesicles and other signalling molecules.[8],[9]

Data Note: For real-world clinical outcomes regarding this specific intrathecal secretome application, please refer to our dedicated data evaluation: ANOVA ALS Real-World Data Report.

Experimental studies suggest that these substances may influence inflammatory processes, support neuronal survival and promote tissue repair mechanisms. Early clinical studies investigating MSC-derived products administered by the intrathecal route have demonstrated encouraging safety data and biological activity, although their clinical efficacy remains under investigation.[6],[7]

At ANOVA IRM, the secretome is administered by lumbar puncture into the cerebrospinal fluid. This route is intended to facilitate direct exposure of the central nervous system to the biologically active components of the preparation. The rationale for this approach is based on current experimental and translational research investigating the interaction between neurotrophic factors and motor neuron survival.

The manufacture of our cellular products is performed under the applicable German regulatory requirements and relevant manufacturing authorisations. Patients receive detailed information regarding the experimental status of this therapeutic approach before treatment.

2. Tauroursodeoxycholic Acid (TUDCA)

Tauroursodeoxycholic acid (TUDCA) is a naturally occurring bile acid that has attracted considerable scientific interest because of its potential neuroprotective properties.[10]

Laboratory studies suggest that TUDCA may influence several biological processes relevant to neurodegenerative diseases, including mitochondrial function, endoplasmic reticulum stress and apoptosis. Early clinical studies in ALS have reported encouraging findings, leading to the initiation of larger international clinical trials designed to further evaluate its therapeutic role.[11],[12]

Where clinically appropriate, TUDCA may be incorporated into an individual treatment plan after careful medical assessment. Its use is based on the available scientific literature, the individual clinical situation and a thorough discussion of the current state of evidence with each patient.

3. Gut Microbiome Assessment

Increasing evidence suggests that communication between the intestinal microbiome and the central nervous system—the so-called gut-brain axis—may influence immune regulation and neurological health.[13],[14]

Several studies have reported differences in the composition of the intestinal microbiome in people living with ALS compared with healthy individuals. Although the precise clinical significance of these observations remains under investigation, they have stimulated growing research interest in the possible contribution of the gut microbiome to neuroinflammatory processes.[15],[16],[17]

For this reason, ANOVA IRM offers comprehensive microbiome analysis as part of an individual clinical assessment. The results may help identify nutritional factors and guide personalised dietary recommendations or probiotic strategies where considered appropriate. These interventions are intended to support general health and are integrated into the overall therapeutic concept after individual medical evaluation.

4. Cellular Senescence and Senolytic Therapies

Biological ageing is increasingly recognised as an important area of research in many neurodegenerative diseases, including ALS.[19]

One focus of current investigation concerns cellular senescence, a biological state in which cells cease to divide while continuing to release inflammatory signalling molecules. Experimental studies suggest that the accumulation of senescent cells may contribute to chronic inflammation and impaired tissue repair.[19],[20]

In animal models and early translational research, senolytic compounds have shown the ability to selectively reduce senescent cell populations and to influence biological markers associated with neurodegeneration. Clinical research evaluating these approaches in human neurodegenerative diseases is ongoing.[18]

Where considered medically appropriate, selected senolytic compounds may be discussed as part of an individual therapeutic concept. Their use is based on the current scientific literature, careful assessment of potential risks and benefits, and comprehensive patient information regarding the investigational nature of these interventions.

Why ANOVA IRM?

ALS remains one of the greatest challenges in modern neurology. Despite significant scientific progress, currently available therapies can only partly address the complex biological processes underlying the disease. This has led to growing international interest in developing translational therapeutic approaches that complement established standards of care.

ANOVA IRM brings together expertise in regenerative medicine, translational research and personalised patient care. Our clinical approach is founded on a careful evaluation of current scientific knowledge together with a comprehensive assessment of each patient's individual medical situation.

Rather than applying a single intervention, we consider a combination of therapeutic strategies that may address different biological mechanisms associated with ALS, including neuroinflammation, neuronal support, cellular ageing and the gut-brain axis. Which components may be appropriate depends on the patient's clinical condition, previous treatments and individual risk-benefit assessment.

Every patient undergoes a detailed medical evaluation before treatment is considered. This includes a review of neurological findings, disease stage, previous therapies, concomitant medical conditions and, where appropriate, additional investigations such as genetic testing or microbiome analysis. Treatment recommendations are developed individually rather than according to a fixed protocol.

We consider close cooperation with the patient's treating neurologist and other healthcare professionals an essential part of responsible clinical care. Open communication, transparent information and careful medical follow-up are integral components of our practice.

Because several of the therapeutic approaches described are not part of established standard treatment for ALS, patients receive detailed information regarding the current state of scientific evidence, potential benefits, possible risks and existing uncertainties before making any treatment decision. Shared decision-making and informed consent are central principles of our clinical practice.

Scientific Foundation

Our therapeutic concepts are informed by findings from basic science, translational research and published clinical studies. The scientific literature cited in this brochure reflects the current state of knowledge relevant to the biological mechanisms addressed by our treatment concepts.

Scientific understanding of ALS continues to evolve rapidly. As new evidence becomes available, therapeutic concepts may be refined to reflect advances in biomedical research and clinical experience.

Important Information

The treatment approaches described in this brochure include interventions that are not currently established as standard therapies for ALS. Some components remain under clinical investigation, and their effectiveness has not yet been confirmed in large randomised clinical trials.

Treatment decisions are made individually following comprehensive medical assessment and discussion of the available scientific evidence. As with all medical interventions, potential benefits cannot be guaranteed, and responses may vary considerably between individuals.

Patients are encouraged to continue regular neurological care. The approaches described by ANOVA IRM are intended to be considered within an integrated medical framework and are not presented as a replacement for guideline-based ALS management.

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-Stage ALS

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 ALS. Patients have to breathe unassistedly and have to be fit for the sedation and brief intervention necessary to harvest fat tissue. 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 adipose tissue (mini-liposuction) requires a 2-day stay in Offenbach, followed by the laboratory isolation of the mesenchymal stromal cells and rigorous quality controls. Approximately 4 weeks after isolation, the individualized application plan can begin. Patients return to our institution in regular intervals determined by their medical requirements. The shelf life of the processed secretome is up to 2 years, allowing for an extended, personalized application schedule based entirely on the patient's individual clinical situation, progression rate, and logistical capacity, which will be thoroughly analyzed during the medical consultations.

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 ALS will cost well 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.

Selected Scientific References

The following peer-reviewed publications provide the scientific background for the biological mechanisms and therapeutic concepts discussed in this brochure. They are intended to support patient information and should not be interpreted as proof of clinical efficacy for any individual treatment approach.

Current Standard Therapy for ALS

  1. Bensimon G, Lacomblez L, Meininger V. A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis. New England Journal of Medicine. 1994;330:585–591.
  2. Miller RG, Mitchell JD, Moore DH. Riluzole for Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND). Cochrane Database of Systematic Reviews. 2012;(3).
  3. Fang T, et al. Riluzole, Disease Stage and Survival in ALS. Lancet Neurology. 2018;17:416–418.
  4. Andrews JA, et al. Real-world Evidence of Riluzole Effectiveness in Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2020;21:509–518.
  5. Thakore NJ, et al. Early Initiation of Riluzole May Improve Absolute Survival in Amyotrophic Lateral Sclerosis. Muscle & Nerve. 2023;67:146–154.

Mesenchymal Stromal Cells and Regenerative Medicine

  1. Oh KW, et al. Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis. Stem Cells Translations Medicine. 2015;4:590–597.
  2. Petrou P, et al. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients with Amyotrophic Lateral Sclerosis. JAMA Neurology. 2016;73:337–344.
  3. Mazzini L, et al. Mesenchymal Stem Cell Transplantation in Amyotrophic Lateral Sclerosis: A Review of Clinical Studies. Journal of Neurology. 2019.
  4. Deng S, Xie H, Xie B. Cell-Based Regenerative and Rejuvenation Strategies for Treating Neurodegenerative Diseases. Stem Cell Research & Therapy. 2025.

TUDCA and Neuroprotection

  1. Cudkowicz ME, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. New England Journal of Medicine. 2022.
  2. Albanese A, et al. Tauroursodeoxycholic Acid in Patients with Amyotrophic Lateral Sclerosis: The TUDCA-ALS Trial Protocol. Frontiers in Neurology. 2022;13:1009113.
  3. Lombardo FL, et al. A Randomised Double-Blind Clinical Trial on Safety and Efficacy of TUDCA as Add-On Treatment in ALS: Statistical Analysis Plan. Trials. 2023;24:792.

Gut–Brain Axis and the ALS Microbiome

  1. Cryan JF, et al. The Microbiota–Gut–Brain Axis. Physiological Reviews. 2019.
  2. Cryan JF, O'Riordan KJ, Cowan CSM, et al. The Microbiota-Gut-Brain Axis. Lancet Neurology. 2020;19:179–194.
  3. Dandamudi S, et al. Neurodegenerative Disorders and the Gut–Microbiome–Brain Axis: A Literature Review. Cureus. 2024.
  4. Li X, et al. Correlation Between the Gut Microbiome and Neurodegenerative Diseases: A Review of Metagenomics Evidence. Neural Regeneration Research. 2024;19:833–845.
  5. Yang EJ. The Emerging Role of the Brain–Gut Axis in Amyotrophic Lateral Sclerosis: Pathogenesis, Mechanisms and Therapeutic Perspectives. International Journal of Molecular Sciences. 2025.

Cellular Senescence and Healthy Ageing

  1. Gonzales MM, et al. Senolytic Therapy in Mild Alzheimer's Disease: A Phase I Feasibility Trial. Nature Medicine. 2023;29:2481–2488.
  2. Tan X, Gao N. The Emerging Role of Cellular Senescence in Amyotrophic Lateral Sclerosis. Frontiers in Neuroscience. 2025.
  3. Tsang VSK, Malaspina A, Henson SM. The Metabolic Intersection Between Immunosenescence and Neuroinflammation in Amyotrophic Lateral Sclerosis. Journal of Inflammation. 2025.

Translational Medicine and Emerging Therapeutic Concepts

  1. Bedlack RS. The Scientific and Therapeutic Rationale for Off-Label Treatments in Amyotrophic Lateral Sclerosis. Annals of Neurology. 2025.
  2. Mejzini R, et al. ALS Genetics, Mechanisms and Therapeutics: Where Are We Now? Frontiers in Neuroscience. 2019.
  3. van Es MA, Hardiman O, Chio A, et al. Amyotrophic Lateral Sclerosis. The Lancet. 2017;390:2084–2098.

Manufacturing authorisation: Regierungspräsidium Hessen & Paul Ehrlich Institut
Treatment under the framework of "individueller Heilversuch" | Information correct as of 2026

Literature and References HAL training for ALS treatment

  1. Nakajima T, Sankai Y, Takata S, Kobayashi Y, Ando Y, Nakagawa M, Saito T, Saito K, Ishida C, Tamaoka A, Saotome T, Ikai T, Endo H, Ishii K, Morita M, Maeno T, Komai K, Ikeda T, Ishikawa Y, Maeshima S, Aoki M, Ito M, Mima T, Miura T, Matsuda J, Kawaguchi Y, Hayashi T, Shingu M, Kawamoto H. Orphanet J Rare Dis. 2021 Jul 7;16(1):304. PMID: 34233722 Free PMC article. Clinical Trial. https://doi/10.1186/s13023-021-01928-9. RESULTS: We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. ...Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, …
  2. Morioka H, Hirayama T, Sugisawa T, Murata K, Shibukawa M, Ebina J, Sawada M, Hanashiro S, Nagasawa J, Yanagihashi M, Uchi M, Kawabe K, Washizawa N, Ebihara S, Nakajima T, Kano O. J Clin Neurosci. 2022 Mar 10;99:158-163. Online ahead of print. PMID: 35279589 Free article. https://doi.org/10.1016/j.jocn.2022.02.032. We used HAL for patients with amyotrophic lateral sclerosis (ALS) to determine whether HAL training had an effect on their gait ability. ...The 10-meter walk test showed significantly improved cadence, although gait speed, step length on the 10-m walk, or ADL …
  3. Sczesny-Kaiser M, Kowalewski R, Schildhauer TA, Aach M, Jansen O, Grasmücke D, Güttsches AK, Vorgerd M, Tegenthoff M. Front Neurosci. 2017 Aug 8;11:449. eCollection 2017. PMID: 28848377 Free PMC article. https://doi.org/10.3389/fnins.2017.00449. Recent studies have shown that the voluntary-driven exoskeleton HAL (hybrid assistive limb) can improve walking functions in spinal cord injury and stroke. The aim of this study was to assess safety and effects on walking function of HAL supported treadmill therapy …

  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).

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)