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Medical Treatments Using Mesenchymal Stem Cells - MSCs

Mesenchymal Stem Cells (MSCs) are one of the most widely studied stem cell types in medicine. They are being investigated in research for a wide range of diseases. The available clinical data are still early and limited, so neither efficacy nor safety in patients can be regarded as established.

At the same time several hundred clinical studies are ongoing to investigate their regenerative abilities in greater detail. From a biological point-of-view, they are progenitor cells of connective tissues. This means that they are important for building and maintaining the healthy status of connective tissues throughout the whole body, and are known as stromal stem cells.

Likewise, they possess the ability to differentiate into a spectrum of other cell types, including chondrocytes (cartilage cells), osteoblasts (bone cells), adipocytes (fat cells), etc. This property classifies them as “multipotent stem cells” (being able to transform into many cell types).

ANOVA IRM Germany MSC mesenchymal stem cell differentiation

MSC proof of nature by differentiation

Why are MSEC - Mesenchymal Stem Cells -
More Often Used Compared Other Stem Cell Types

There are several reasons of why they are the leading stem cell type in medical applications and clinical trials on humans:

  • They are relatively easy to harvest and be isolated from:

    • Fat tissue, known as adMSCs (adipose derived MSCs)
    • Bone Marrow, known as bmMSCs (bone marrow MSCs)
    • Umbilical Cord, known as ucMSC (umbilical cord MSCs)
  • MSCs are relatively stable to culture and expand in the laboratory
  • They can go through relatively many division cycles without losing their expression profile, health and division potential
  • Numerous animal, clinical and scientific data collected for various disease models, including neurodegenerative diseases
  • Laboratory studies so far report a low tendency of MSCs to form tumour cells; long-term safety in patients is still being investigated
  • Recent laboratory research is investigating the stem cell secretome profile, which has shown a range of regenerative and protective activities in preclinical models
  • As such, MSCs are our favorite source for making our Stem Cell Secretome therapies.

MSC Isolated From Fat Tissue

Fat tissue contain MSCs in relatively high concentration. The tissue is processed by enzymatic or microscopical removal of non-cellular parts. This cellular end product is called Stromal Vascular Fraction (SVF). SVF has been examined in early clinical research for certain areas and diseases; these findings are preliminary. In addition, the amount of MSCs it contains is limited. Expansion of MSCs (increasing their cell count in the laboratory) is relatively straightforward. However, this process drastically complicates the clinical application because it impacts the risk profile as well. Due to this fact, this process is highly restricted in all developed countries. Research suggests that the decisive factor may not be a high cell count as such, but rather the viability and the secretion profile of the cells.

All this knowledge lead the scientists of our German Stem Cell Clinic to pursue a different approach to Stem Cell treatments: The Stem Cell Secretome. The secretome contains active components, e.g. growth factors and cytokines, which are being studied in laboratory research as possible mediators of the regenerative effects observed in preclinical models.

MSC mesenchymal stem cell flourecent microscope image wide

Confocal microscopy image of Mesenchymal Stem Cells (MSCs) with florescence staining

ANOVA applies Stem Cell Secretome Therapy for patients from all over the world. For more information on secretome (stem cell-based) treatments, please feel free to contact us.

What Is Research Investigating About the Potential of Mesenchymal Stem Cells?

Properties of Mesenchymal Stem Cells MSC investigated in research

The Figure illustrates properties of MSCs as described in the scientific literature. Research is investigating several properties of MSCs: 1) the capacity to differentiate into various cell lineages, 2) the secretion of paracrine factors, which are being studied for a possible role in healing and regeneration in surrounding cells, 3) possible effects on inflammation and immune regulation observed in laboratory studies, 4) migration towards sites of injury described in preclinical models. Figure from [10].

Stem Cell Therapies sorted by stem cell type (source tissue) and product

 

Overview

Numerous types of stem cell therapies are available at ANOVA. Stem cell research brought insights that allowed for technological advancements in therapies and expanding the knowledge of the underlying mechanisms of stem cells. This has allowed for more effective therapies to be developed.

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BMC

Bone Marrow Concentrate (BMC) is one of the most commonly applied source of stem cells. Despite the fact that the actual number of stem cells in BMC is biologically limited, several other (regenerative) factors in BMC have been shown to deliver promising results in the treatment of numerous diseases.

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Stem Cell Secretome

Stem Cell Therapies 2.0: The ANOVA Stem Cell Secretome Therapy is the next generation of stem cell-based therapies. It was designed to harness and mass produce the healing essences of stem cells (paracrine and regenerative factors, extracellular vesicles, exosomes) in a uniquely designed laboratory process..

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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)

References and Literature - Mesenchymal Stem Cells 'MSCs'

  1. Gu W, Zhang F, Xue Q, Ma Z, Lu P, Yu B. Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord. Neuropathology. 2010; 30: 205-217.
  2. Wilkins A, Kemp K, Ginty M, Hares K, Mallam E, Scolding N. Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res. 2009; 3: 6370
  3. Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin. 2013; 34: 747-754.
  4. Wang S, Qu X, Zhao RC. Clinical applications of mesenchymal stem cells. J Hematol Oncol. 2014; 5: 19.
  5. Farini, Andrea, et al. "Clinical applications of mesenchymal stem cells in chronic diseases." Stem cells international 2014 (2014).
  6. Volarevic, Vladislav, et al. "Concise review: therapeutic potential of mesenchymal stem cells for the treatment of acute liver failure and cirrhosis." Stem Cells 32.11 (2014): 2818-2823.
  7. Ikebe, Chiho, and Ken Suzuki. "Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols." BioMed research international 2014 (2014).
  8. Sharma, Ratti Ram, et al. "Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices." Transfusion 54.5 (2014): 1418-1437.
  9. Jo, Chris Hyunchul, 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 32.5 (2014): 1254-1266.
  10. Squillaro, Tiziana, Gianfranco Peluso, and Umberto Galderisi. "Clinical trials with mesenchymal stem cells: an update." Cell transplantation 25.5 (2016): 829-848.
  11. Orozco, Lluis, et al. "Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results." Transplantation 97.11 (2014): e66-e68.
  12. Filardo, Giuseppe, et al. "Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics." Knee surgery, sports traumatology, arthroscopy 21.8 (2013): 1717-1729.
  13. Jo, Chris Hyunchul, 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 32.5 (2014): 1254-1266.
  14. Vangsness, C. Thomas, et al. "Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy." J Bone Joint Surg Am 96.2 (2014): 90-98.
  15. Pires A.O., Mendes-Pinheiro B., Teixeira F.G., Anjo S.I., Ribeiro-Samy S., Gomes E.D., Serra S.C., Silva N.A., Manadas B., Sousa N., et al. Unveiling the Differences of Secretome of Human Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Stem Cells, and Human Umbilical Cord Perivascular Cells: A Proteomic Analysis. Stem Cells Dev. 2016;25:1073–1083. doi: 10.1089/scd.2016.0048.

  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.
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  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).
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  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.
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  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.
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  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.
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  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
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  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.
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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