ANOVA's Stem Cell Secretome Therapy

ANOVA's Stem Cell Secretome Therapy

The use of stem cells is still heavily restricted in most countries. This has severely limited their use in medicine despite their proven effectiveness in treating many chronic or uncurable diseases.

This may change now with one of the latest breakthroughs in stem cell research. ANOVA's team has implemented a scientific process that elegantly and efficiently harvests and concentrates the therapeutic components produced by stem cells that are responsible for the stem cells' healing power. Stem cells harvested from the patient's own tissue can now be grown and expanded in vitro in the laboratory. The aim of this process is to induce the production of the specific regenerative substances (cytokines, microRNAs, growth factors, etc.) that stem cells are secreting, to concentrate them and utilize them for the treatment of the condition that the patient is suffering from. Instead of reimplanting stem cells into patients for the purpose of healing them, only the secreted cellular active components are reinjected in order to make the therapy potent and effective. Compared to the reimplantation of stem cells, the risk of using this method is relatively small.

Flowchart ANOVA 7 Steps SCS 2

Step 01 450x550
Step 02 450x550

Step 2 - Processing the stem cells and production of the Stem Cell Secretome (SCS)

In our specialized laboratories, the “stromal vascular fraction” (SVF) is isolated from adipose tissue after enzymatic digestion. The SVF is a mixture of different types of cells. It contains a high percentage of MSCs (equivalent of up to 500.000 cells per gram), and is one of the highest amounts of MSCs to be found in the human body.

By subjecting the cells to external stimuli, they can be stimulated to secrete a high concentration of cytokines, micro-RNAs and growth factors (that retain regenerative abilities) that are packed in extracellular vesicles (microvesicles and exosomes). Together, these factors make up the secretome.

In the next step the cells are laboratory grown and expanded, where the MSCs are obtained by special technique. These MSCs can now be used for the mass production of the Mesenchymal Stem Cell Secretome (MSEC). MSEC consists of a high concentration of the extremely effective healing substances that are secreted by the MSCs.

The stem cell secretome is ready for use, and can be stored for several months at minus 80°C. This makes it possible to design a therapy plan that allows for several infusions (over several years) and favors optimal treatment outcomes possible.

Step 03 450x550

Advantages and Applications
ANOVA Stem Cell Secretome Therapy

Advantages

  • The Secretome is devoid of all cells which will decrease the risk of unwanted reactions in allogeneic use.
  • The Secretome has been tested in an autologous setting in hundreds of patients without any detrimental side effects.
  • Therapeutic doses can be achieved with as little as 1 million of mesenchymal stem cells.
  • The Stem Cell Secretome ready for use can be stored at minus 80°C without any siginificant loss of activity or quality.
  • Up to ten therapeutic doses of Stem Cell Secretome are available for a therapy course without renewed Stem Cell isolation.
  • ANOVA Stem Cell Secretome therapy can be carried out at regular intervals over extended periods of time, e.g. at weekly intervals, providing a treatment courses instead of a single treatment at only one time point.

Applications

References and Literature -  (Click for more)

If you are interested to receive the list of references, please contact us.

References and Literature - Stem Cell Secretome (Click for more)

  1. Konala, Vijay Bhaskar Reddy, et al. "The current landscape of the mesenchymal stromal cell secretome: a new paradigm for cell-free regeneration." Cytotherapy 18.1 (2016): 13-24.
  2. Lopez-Verrilli, M. A., et al. "Mesenchymal stem cell-derived exosomes from different sources selectively promote neuritic outgrowth." Neuroscience 320 (2016): 129-139.
  3. Kim, Hyun Ok, Seong-Mi Choi, and Han-Soo Kim. "Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders." Tissue Engineering and Regenerative Medicine 10.3 (2013): 93-101.
  4. Rani, Sweta, et al. "Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications." Molecular Therapy 23.5 (2015): 812-823.
  5. Zhang, Xiaoyan, et al. "Mesenchymal Stem Cell-Derived Extracellular Vesicles: Roles in Tumor Growth, Progression, and Drug Resistance." Stem Cells International 2017 (2017).
  6. omzikova, Marina O., and Albert A. Rizvanov. "Current Trends in Regenerative Medicine: From Cell to Cell-Free Therapy." BioNanoScience (2016): 1-6.
  7. Zhang, Bin, et al. "Focus on extracellular vesicles: Therapeutic potential of stem cell-derived extracellular Vesicles." International journal of molecular sciences 17.2 (2016): 174.
  8. Katsuda T. et al. (2013). Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Scientific reports, 3, 1197.
  9. Pusic A. D. et al. (2014). IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. Journal of neuroimmunology, 266(1), 12-23.
  10. Maumus M, Jorgensen C, Noël D (2013) Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: Role of secretome and exosomes. Biochimie 95:2229–2234. doi: 10.1016/j.biochi.2013.04.017
  11. Drago D, Cossetti C, Iraci N, et al (2013) Biochimie The stem cell secretome and its role in brain repair. Biochimie 95:2271–2285. doi: 10.1016/j.biochi.2013.06.020
  12. Sevivas N, Teixeira FG, Portugal R, et al (2016) Mesenchymal Stem Cell Secretome: A Potential Tool for the Prevention of Muscle Degenerative Changes Associated With Chronic Rotator Cuff Tears. Am J Sports Med. doi: 10.1177/0363546516657827
  13. Hs K (2016) Mesenchymal Stem Cells vs . Mesenchymal Stem Cell Secretome for Rheumatoid Arthritis Treatment. 1:1–2.
  14. Maumus M, Jorgensen C, Noël D (2013) Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: Role of secretome and exosomes. Biochimie 95:2229–2234. doi: 10.1016/j.biochi.2013.04.017
  15. Kapur SK, Katz AJ (2013) Biochimie Review of the adipose derived stem cell secretome. Biochimie 95:2222–2228. doi: 10.1016/j.biochi.2013.06.001
  16. Ranganath SH, Levy O, Inamdar MS, Karp JM (2012) Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell 10:244–258. doi: 10.1016/j.stem.2012.02.005
  17. Tran C, Damaser MS (2015) Stem cells as drug delivery methods: Application of stem cell secretome for regeneration. Adv Drug Deliv Rev 82:1–11. doi: 10.1016/j.addr.2014.10.007
  18. Zimmerlin L, Park TS, Zambidis ET, et al (2013) Mesenchymal stem cell secretome and regenerative therapy after cancer. Biochimie 95:2235–2245. doi: 10.1016/j.biochi.2013.05.010
  19. Calamia V, Lourido L, Fernandez-Puente P, et al (2012) Secretome analysis of chondroitin sulfate-treated chondrocytes reveals its anti-angiogenic, anti-inflammatory and anti-catabolic properties. Arthritis Res Ther 14:R202. doi: 10.1186/ar4040
  20. Ranganath SH, Levy O, Inamdar MS, Karp JM (2012) Review Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease. Stem Cell 10:244–258. doi: 10.1016/j.stem.2012.02.005
  21. Teixeira FG, Carvalho MM, Sousa N, Salgado AJ (2013) Mesenchymal stem cells secretome: A new paradigm for central nervous system regeneration? Cell Mol Life Sci 70:3871–3882. doi: 10.1007/s00018-013-1290-8
  22. Kapur SK, Katz AJ (2013) Review of the adipose derived stem cell secretome. Biochimie 95:2222–2228. doi: 10.1016/j.biochi.2013.06.001
  23. Chang C-P, Chio C-C, Cheong C-U, et al (2013) Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci (Lond) 124:165–76. doi: 10.1042/CS20120226
  24. Salgado AJ, Sousa JC, Costa BM, et al (2015) Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic insights and therapeutic opportunities. Front Cell Neurosci 9:1–18. doi: 10.3389/fncel.2015.00249
  25. Ahmed NE-MB, Murakami M, Hirose Y, Nakashima M (2016) Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study. Stem Cells Int 2016:8102478. doi: 10.1155/2016/8102478
  26. Bhaskar V, Konala R, Mamidi MK, et al (2016) The current landscape of the mesenchymal stromal cell secretome : A new paradigm for cell-free regeneration. Cytotherapy 18:13–24. doi: 10.1016/j.jcyt.2015.10.008
  27. Malda J, Boere J, van de Lest C, et al (2016) Extracellular vesicles - new tool for joint repair and regeneration - IN PRESS. Nat Rev Rheumatol 12:243–249. doi: 10.1038/nrrheum.2015.170
  28. Lener T, Gimona M, Aigner L, et al (2015) Applying extracellular vesicles based therapeutics in clinical trials Á an ISEV position paper. 1:1–31.
  29. Dostert G, Mesure B, Menu P, Velot É (2017) How Do Mesenchymal Stem Cells Influence or Are Influenced by Microenvironment through Extracellular Vesicles Communication ? 5:1–7. doi: 10.3389/fcell.2017.00006
  30. Joshi P, Benussi L, Furlan R, et al (2015) Extracellular vesicles in Alzheimer’s disease: Friends or foes? focus on Aβ-vesicle interaction. Int. J. Mol. Sci. 16:4800–4813.
  31. Gao T, Guo W, Chen M, et al (2016) Extracellular Vesicles and Autophagy in Osteoarthritis.
  32. Katsuda T, Ochiya T (2015) Molecular signatures of mesenchymal stem cell-derived extracellular vesicle-mediated tissue repair. Stem Cell Res Ther 6:212. doi: 10.1186/s13287-015-0214-y
  33. Lener T, Gioma M, Aigner L, et al (2015) Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles 4:1–31. doi: 10.3402/jev.v4.30087
  34. Xu Y, Guo S, Wei C, et al (2016) The Comparison of Adipose Stem Cell and Placental Stem Cell in Secretion Characteristics and in Facial Antiaging.
  35. Buul GM Van, Villafuertes E, Bos PK, et al (2012) Mesenchymal stem cells secrete factors that inhibit in fl ammatory processes in short-term osteoarthritic synovium and cartilage explant culture. Osteoarthr Cartil 20:1186–1196. doi: 10.1016/j.joca.2012.06.003
  36. Baglio SR, Pegtel DM, Baldini N (2012) Mesenchymal stem cell secreted vesicles provide novel opportunities in ( stem ) cell-free therapy. 3:1–11. doi: 10.3389/fphys.2012.00359
  37. Anderson JD, Pham MT, Contreras Z, et al (2016) Mesenchymal stem cell-based therapy for ischemic stroke. Chinese Neurosurg J 2:36. doi: 10.1186/s41016-016-0053-4
  38. Biology C, Cell R, Eye N, Institutes N (2017) Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms. 1273–1285.

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