Cellular Therapy in the Treatment of Musculoskeletal Disorders

  • О. V. Banit Zaporizhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine, Zaporizhzhia, Ukraine
DOI: https://doi.org/10.30702/transpaorg/02_21.3103/0969-82/576.36
Keywords: musculoskeletal disorder, mesenchymal stem (stromal) cells, stromal-vascular fraction, cell-based medicinal products from adipose tissue

Abstract

The number of injuries and diseases of the musculoskeletal system is constantly increasing every year. Given the world’s population aging, more and more attention is paid to disease prevention and the development of specific treatment options. Recently, there has been a dynamic growth of cell technology.
The aim. To evaluate the safety and effectiveness of cell-based medicinal products from adipose tissue for the treatment of musculoskeletal disorders and compare them with each other.
Materials and methods. In 2018-2020, at the premises of the Department of Traumatology and Orthopedics of Zaporizhia Medical Academy of Post-Graduate Education of the Ministry of Health of Ukraine and the Department of Orthopedics, Aesthetic and Regenerative Medicine of Vitacenter General Hospital, 45 patients with orthopedic disorders were treated using cell-based medicinal products made from native adipose tissue.
In 40 cases, stromal-vascular fraction obtained from native adipose tissue using various devices (Goisis, Regenlab, Arthrex SVF, Lipogems®) was injected. Five patients were treated with cultured autologous chondrocytes and multipotent mesenchymal stromal cells from adipose tissue obtained in collaboration with a specialized laboratory “Ilaya.regeneration”, Kyiv.
Results and discussion. In the first group, 4 patients had no adverse reactions, only one patient after administration had manifestations of gonarthritis with subsequent improvement.
No patients had adverse reactions to the introduction of stromal-vascular fraction. Patientsof both groups were observed for 3-5 days after the procedure, and then once a month; the assessment was performed using VAS, IKDC, WOMAC, KOOS, KSS. All the patients showed gradual decrease in pain improved joint function, and improved quality of life. It is probably incorrect to compare these groups in terms of the number of patients, but we saw a similar pattern in clinical manifestations in both groups. Our observations showed a difference only in the duration of positive changes noted by patients. In the group of patients who received cellbased medicinal product from the stromal-vascular fraction, the positive effect gradually decreased within 1.5-2 years. After the introduction of cultured cell-based products in patients, their clinical condition improved to a level that was maintained for 3 years without significant changes

References

  1. Aguena M, Fanganiello RD, Tissiani LA, Ishiy FA, Atique R, Alonso N, et al. Optimization of parameters for a more efficient use of adipose-derived stem cells in regenerative medicine therapies. Stem Cells Int. 2012;2012:303610. https://doi.org/10.1155/2012/303610.
  2. Aronowitz J, Ellenhorn J. Adipose stromal vascular fraction isolation: A head-to-head comparison of four commercial cell separation systems. Plast Reconstr Surg. 2013 Dec;132(6):932e-939e. https://doi.org/10.1097/PRS.0b013e3182a80652.
  3. Aronowitz JA, Lockhart RA, Hakakian CS, Hicok KC. Clinical safety of stromal vascular fraction separation at the point of care. Ann Plast Surg. 2015 Dec;75(6):666-71. https://doi.org/10.1097/SAP.0000000000000594.
  4. Aronowitz J, Lockhart R, Hakakian С. Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springer Plus. 2015;4:713. https://doi.org/10.1186/s40064-015-1509-2 5.
  5. Baer P, Geiger H. Adipose-derived mesenchymal stromal/stem cells: Tissue localization, characterization, and heterogeneity. Stem Cell Int. 2012;2012:812693. https://doi.org/10.1155/2012/812693.
  6. Baptista LS, do Amaral RJ, Carias RB, Aniceto M, Claudio-da-Silva C, Borojevic R. An alternative method for the isolation of mesenchymal stromal cells derived from lipoaspirate samples. Cytotherapy. 2009;11(6):706-15. https://doi.org/10.3109/14653240902981144.
  7. Belova AN, Shchepetova ON. Shkaly, testy i oprosniki v medicinskoj reabilitacii [Labs, tests and questionnaires are in medical rehab]. Moscow; 2002.
  8. Burlacu A, Grigorescu G, Rosca AM, Preda MB, Simionescu M. Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells and Development. 2013 Feb 15;22(4):643-53. https://doi.org/10.1089/scd.2012.0273.
  9. Caplan AI. All MSCs are pericytes? Cell Stem Cell. 2008 Sep 11;3(3):229-30. https://doi.org10.1016j.stem.2008.08.008.
  10. Casiraghi F, Remuzzi G, Abbate M, Perico N. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev Rep. 2013 Feb;9(1):65-79. https://doi.org/10.1007/s12015-011-9345-4.
  11. Cawthorn WP, Scheller EL, MacDougald OA. Adipose tissue stem cells meet preadipocyte commitment: Going back to the future. J Lipid Res. 2012 Feb;53(2):227-46. https://doi.org/10.1194/jlr.R021089.
  12. Coleman WP 3rd, Glogau RG, Klein JA, Moy RL, Narins RS, Chuang TY, Farmer ER, et al. Guidelines of care for liposuction. J Am Acad Dermatol. 2001 Sep;45(3):438-47. https://doi.org/10.1067/mjd.2001.117045.
  13. Ebrahimi A, Kazemi A, Rasouli HR, Kazemi M, Kalantar Motamedi MH. Reconstructive surgery of auricular defects: An overview. Trauma Mon. 2015 Nov;20(4):e28202. https://doi.org/10.5812/traumamon.28202.
  14. Escacena N, Quesada-Hernández E, Capilla-Gonzalez V, Soria B, Hmadcha A. Bottlenecks in the efficient use of advanced therapy medicinal products based on mesenchymal stromal cells. Stem Cells International. 2015;2015:895714. https://doi.org/10.1155/2015/895714. Epub 2015 Jul 27.
  15. Fraser JK, Hicok KC, Shanahan R, Zhu M, Miller S, Arm DM. The Celution® system: Automated processing of adipose-derived regenerative cells in a functionally closed system. Adv Wound Care. 2014 Jan 1;3(1):38-45. https://doi.org/10.1089/wound.2012.0408.
  16. Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet. 1987 May;20(3):263-72. https://doi.org/10.1111/j.1365-2184.1987.tb01309.x.
  17. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007 May 11;100(9):1249-60. https://doi.org/10.1161/01.RES.0000265074.83288.09.
  18. Han J, Koh YJ, Moon HR, Ryoo HG, Cho CH, Kim I, et al. Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood. 2010 Feb 4;115(5):957-64. https://doi.org/10.1182/blood-2009-05-219923.
  19. Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, et al. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol. 2010 Dec;10(12):1496-500. https://doi.org/10.1016/j.intimp.2010.06.019.
  20. Jin R, Zhang L, Zhang YG. Does platelet-rich plasma enhance the survival of grafted fat? An update review. Int J Clin Exp Med. 2013 Apr 12;6(4):252-8.
  21. Kato H, Mineda K, Eto H, Doi K, Kuno S, Kinoshita K, et al. Degeneration, regeneration, and cicatrization after fat grafting: Dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg. 2014 Mar;133(3):303e-313e. https://doi.org/10.1097/PRS.0000000000000066.
  22. Kilroy GE, Foster SJ, Wu X, Ruiz J, Sherwood S, Heifetz A, et al. Cytokine profile of human adiposederived stem cells: Еxpression of angiogenic, hematopoietic, and pro-inflammatory factors. J Cell Physiol. 2007 Sep;212(3):702-9. https://doi.org/10.1002/jcp.21068.
  23. Kyryk VM, Butenko GM. Stvolovye kletki iz zhirovoj tkani: osnovnye harakteristiki i perspektivy klinicheskogo primeneniya v regenerativnoj medicine (obzor literatury) [Fat stem cells: basic characteristics and prospects for clinical use in regenerative medicine (literature review)]. Zhurnal Akademії medichnikh nauk Ukrainy. 2010;16(4):576-604. Russian.
  24. Kronsteiner B, Wolbank S, Peterbauer A, Hackl C, Redl H, van Griensven M, et al. Human mesenchymal stem cells from adipose tissue and amnion influence T-cells depending on stimulation method and presence of other immune cells. Stem Cells Dev. 2011 Dec;20(12):2115-26. https://doi.org/10.1089/scd.2011.0031.
  25. Lee SK, Kim DW, Dhong ES, Park SH, Yoon ES. Facial soft tissue augmentation using autologous fat mixed with stromal vascular fraction. Arch Plast Surg. 2012 Sep;39(5):534-9. https://doi.org/10.5999/aps.2012.39.5.534.
  26. Minteer DM, Marra KG, Rubin JP. Adipose stem cells: biology, safety, regulation, and regenerative potential. Clin Plastic Surg. 2015 Apr;42(2):169-79. https://doi.org/10.1016/j.cps.2014.12.007.
  27. Oberbauer E, Steffenhagen C, Wurzer C, Gabriel C, Redl H, Wolbank S. Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: Current state of the art. Cell Regen. 2015 Sep 30;4:7. https://doi.org/10.1186/s13619-015-0020-0.
  28. Pappa AK, Caballero M, Dennis RG, Skancke MD, Narayan RJ, Dahl JP, et al. Biochemical properties of tissue-engineered cartilage. J Craniofac Surg. 2014 Jan;25(1):111-5. https://doi.org/10.1097/SCS.0b013e3182a2eb56.
  29. Rajashekhar G, Traktuev DO, Roell WC, Johnstone BH, Merfeld-Clauss S, Van Natta B,, et al. IFATS collection: Adipose stromal cell differentiation is reduced by endothelial cell contact and paracrine communication: role of canonical Wnt signaling. Stem Cells. 2008 Oct;26(10):2674-81. https://doi.org/10.1634/stemcells.2008-0277.
  30. Salgado AJ, Reis RL, Sousa NJ, Gimble JM. Adipose tissue derived stem cells secretome: Soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010 Jun;5(2):103-10. https://doi.org/10.2174/157488810791268564.
  31. Shah FS, Wu X, Dietrich M, Rood J, Gimble JM. A non-enzymatic method for isolating human adipose tissue-derived stromal stem cells. Cytotherapy. 2013 Aug;15(8):979-85. https://doi.org/10.1016/j.jcyt.2013.04.001.
  32. Suga H, Eto H, Aoi N, Kato H, Araki J, Doi K, et al. Adipose tissue remodeling under ischemia: Death of adipocytes and activation of stem/progenitor cells. Plast Reconstr Surg. 2010 Dec;126(6):1911-1923. https://doi.org/10.1097/PRS.0b013e3181f4468b.
  33. Tobita M, Orbay H, Mizuno H. Adipose-derived stem cells: current findings and future perspectives. Discov Med. 2011 Feb;11(57):160-70.
  34. Tobita M, Tajima S, Mizuno H. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: Stem cell transplantation methods that enhance stemness. Stem Cell Res & Ther. 2015 Nov 5;6:215. https://doi.org/10.1186/s13287-015-0217-8.
  35. Zhu M, Zhou Z, Chen Y, Schreiber R, Ransom JT, Fraser JK, et al. Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention. Ann of Plastic Surg. 2010 Feb;64(2):222-8. https://doi.org/10.1097/SAP.0b013e31819ae05c.
  36. Zimmerlin L, Donnenberg VS, Pfeifer ME, Meyer EM, Péault B, Rubin JP, et al. Stromal vascular progenitors in adult human adipose tissue. Cytometry Part A: J Int Soc Anal Cytol. 2010 Jan;77(1):22-30. https://doi.org/10.1002/cyto.a.20813.
  37. Zorina A, Zorin V, Cherkasov V. [PRP in aesthetic medicine]. Experimentation and wedge dermatocometol. 2013;6:10-21. Russian.
  38. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002 Dec;13(12):4279-95. https://doi.org/10.1091/mbc.e02-02-0105.
  39. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue engineering. 2001 Apr;7(2):211-28. https://doi.org/10.1089/107632701300062859
Published
2021-03-31
How to Cite
BanitО. V. (2021). Cellular Therapy in the Treatment of Musculoskeletal Disorders. Transplantation and Artificial Organs, (1(02), 69-82. https://doi.org/10.30702/transpaorg/02_21.3103/0969-82/576.36
Issue
Transplantation and artificial organs №1(02) 2021
Section
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