Frontiers in veterinary science2020; 7; 554306; doi: 10.3389/fvets.2020.554306

Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells.

Abstract: Extracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells, and decrease inflammatory and immune reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies . Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation toward the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.
Publication Date: 2020-12-04 PubMed ID: 33344521PubMed Central: PMC7746774DOI: 10.3389/fvets.2020.554306Google Scholar: Lookup
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  • Journal Article

Summary

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This study explores the effects of Extracorporeal Shock Wave Therapy (ESWT) on equine Umbilical Cord Blood Mesenchymal Stromal Cells (CB-MSCs). The research found that ESWT enhances the metabolic activity and differentiation of these cells, but does not affect their immunosuppressive properties.

Understanding the Objective and Significance of the Research

  • The main objective of this paper was to investigate the impact of ESWT on equine CB-MSCs. The research specifically aimed to determine the proliferative, metabolic, migratory, differentiative, and immunomodulatory effects of ESWT on these cells.
  • This study is significant because it offers insight into possible synergies between ESWT and CB-MSC therapies in treating musculoskeletal injuries. Moreover, while these therapies have been combined clinically to treat tendon and ligament lesions in horses, there had previously been no scientific evidence backing the effectiveness or influence of this combination.

An Overview of Methods and Experimentation

  • The researchers used equine CB-MSC cultures from independent donors and applied ESWT using an electrohydraulic shock wave generator. These experiments were performed in triplicate to insure accuracy and reliability.
  • After ESWT treatment, the researchers evaluated the proliferation, viability, migration, and immunomodulatory properties of the cells. They also evaluated the potential for trilineage differentiation (into adipocyte, osteocyte, and chondrocyte lineages).

Interpreting the Findings

  • The study found that ESWT treatment led to increased metabolic activity in the CB-MSCs. These cells also showed positive adipogenic, osteogenic, and chondrogenic differentiation, meaning they were more likely to transform into fat cells, bone cells, and cartilage cells respectively, after ESWT treatment.
  • While there was an increase in the differentiation potential of the cells towards adipogenic and osteogenic cell fates, the immunomodulatory properties of the cells remained unaltered after ESWT treatment.
  • Hence, it appears that ESWT promotes increased metabolic activity and has positive influence on the differentiation of equine CB-MSCs, but has no observable impact on their immunosuppressive characteristics.

Implications and Further Studies

  • The results of this study provide the first scientific evidence supporting the combined use of ESWT and CB-MSCs therapy, a treatment commonly given to horses for tendon and ligament injuries.
  • The researchers suggest that more studies are needed to fully understand if these combined therapies could provide synergistic benefits for the treatment of musculoskeletal injuries.

Cite This Article

APA
Salcedo-Jimu00e9nez R, Koenig JB, Lee OJ, Gibson TWG, Madan P, Koch TG. (2020). Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells. Front Vet Sci, 7, 554306. https://doi.org/10.3389/fvets.2020.554306

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 7
Pages: 554306
PII: 554306

Researcher Affiliations

Salcedo-Jimu00e9nez, Ramu00e9s
  • Department of Clinical Studies, University of Guelph, Guelph, ON, Canada.
Koenig, Judith B
  • Department of Clinical Studies, University of Guelph, Guelph, ON, Canada.
Lee, Olivia J
  • Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Gibson, Thomas W G
  • Department of Clinical Studies, University of Guelph, Guelph, ON, Canada.
Madan, Pavneesh
  • Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Koch, Thomas G
  • Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.

Conflict of Interest Statement

TK acts in a volunteer capacity as non-executive Director, Scientific Affairs (ex officio) of eQcell therapies Inc., Aurora, ON, Canada, a company for which TK's research laboratory provides equine stem cell isolation and storage services. TK holds a minor non-controlling share in eQcell therapies Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 30 references
  1. Ioppolo F, Rompe JD, Furia JP, Cacchio A. Clinical application of shock wave therapy (SWT) in musculoskeletal disorders.. Eur J Phys Rehabil Med 2014 Apr;50(2):217-30.
    pubmed: 24667365
  2. Chamberlain GA, Colborne GR. A review of the cellular and molecular effects of extracorporeal shockwave therapy.. Vet Comp Orthop Traumatol 2016;29(2):99-107.
    doi: 10.3415/VCOT-15-04-0057pubmed: 26846274google scholar: lookup
  3. Bosch G, de Mos M, van Binsbergen R, van Schie HT, van de Lest CH, van Weeren PR. The effect of focused extracorporeal shock wave therapy on collagen matrix and gene expression in normal tendons and ligaments.. Equine Vet J 2009 Apr;41(4):335-41.
    doi: 10.2746/042516409X370766pubmed: 19562893google scholar: lookup
  4. Revenaugh MS. Extracorporeal shock wave therapy for treatment of osteoarthritis in the horse: clinical applications.. Vet Clin North Am Equine Pract 2005 Dec;21(3):609-25, vi.
    doi: 10.1016/j.cveq.2005.09.001pubmed: 16297724google scholar: lookup
  5. Ogden JA, Tu00f3th-Kischkat A, Schultheiss R. Principles of shock wave therapy.. Clin Orthop Relat Res 2001 Jun;(387):8-17.
  6. McClure S, Weinberger T. Extracorporeal shock wave therapy: clinical applications and regulation. Clin. Tech. Equine Pract. (2003) 2:358u201367. 10.1053/j.ctep.2004.04.007
  7. Suhr F, Delhasse Y, Bungartz G, Schmidt A, Pfannkuche K, Bloch W. Cell biological effects of mechanical stimulations generated by focused extracorporeal shock wave applications on cultured human bone marrow stromal cells.. Stem Cell Res 2013 Sep;11(2):951-64.
    doi: 10.1016/j.scr.2013.05.010pubmed: 23880536google scholar: lookup
  8. Schuh CM, Heher P, Weihs AM, Banerjee A, Fuchs C, Gabriel C, Wolbank S, Mittermayr R, Redl H, Ru00fcnzler D, Teuschl AH. In vitro extracorporeal shock wave treatment enhances stemness and preserves multipotency of rat and human adipose-derived stem cells.. Cytotherapy 2014 Dec;16(12):1666-78.
    doi: 10.1016/j.jcyt.2014.07.005pubmed: 25174738google scholar: lookup
  9. Raabe O, Shell K, Goessl A, Crispens C, Delhasse Y, Eva A, Scheiner-Bobis G, Wenisch S, Arnhold S. Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived mesenchymal stem cells in vitro.. Am J Stem Cells 2013;2(1):62-73.
    pmc: PMC3636727pubmed: 23671817
  10. Weihs AM, Fuchs C, Teuschl AH, Hartinger J, Slezak P, Mittermayr R, Redl H, Junger WG, Sitte HH, Ru00fcnzler D. Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation.. J Biol Chem 2014 Sep 26;289(39):27090-27104.
    doi: 10.1074/jbc.M114.580936pmc: PMC4175346pubmed: 25118288google scholar: lookup
  11. Caplan AI, Bruder SP. Mesenchymal stem cells: building blocks for molecular medicine in the 21st century.. Trends Mol Med 2001 Jun;7(6):259-64.
    doi: 10.1016/S1471-4914(01)02016-0pubmed: 11378515google scholar: lookup
  12. Gutierrez-Nibeyro SD. Commercial cell-based therapies for musculoskeletal injuries in horses.. Vet Clin North Am Equine Pract 2011 Aug;27(2):363-71.
    doi: 10.1016/j.cveq.2011.04.001pubmed: 21872764google scholar: lookup
  13. Li T, Xia M, Gao Y, Chen Y, Xu Y. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy.. Expert Opin Biol Ther 2015;15(9):1293-306.
    doi: 10.1517/14712598.2015.1051528pubmed: 26067213google scholar: lookup
  14. Mattar P, Bieback K. Comparing the Immunomodulatory Properties of Bone Marrow, Adipose Tissue, and Birth-Associated Tissue Mesenchymal Stromal Cells.. Front Immunol 2015;6:560.
    doi: 10.3389/fimmu.2015.00560pmc: PMC4630659pubmed: 26579133google scholar: lookup
  15. Chang CL, Chen HH, Chen KH, Chiang JY, Li YC, Lin HS, Sung PH, Yip HK. Adipose-derived mesenchymal stem cell-derived exosomes markedly protected the brain against sepsis syndrome induced injury in rat.. Am J Transl Res 2019;11(7):3955-3971.
    pmc: PMC6684905pubmed: 31396312
  16. Johnson V, Webb T, Norman A, Coy J, Kurihara J, Regan D, Dow S. Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections.. Sci Rep 2017 Aug 29;7(1):9575.
    doi: 10.1038/s41598-017-08311-4pmc: PMC5575141pubmed: 28851894google scholar: lookup
  17. Koch TG, Heerkens T, Thomsen PD, Betts DH. Isolation of mesenchymal stem cells from equine umbilical cord blood.. BMC Biotechnol 2007 May 30;7:26.
    doi: 10.1186/1472-6750-7-26pmc: PMC1904213pubmed: 17537254google scholar: lookup
  18. Holfeld J, Tepeku00f6ylu00fc C, Kozaryn R, Mathes W, Grimm M, Paulus P. Shock wave application to cell cultures.. J Vis Exp 2014 Apr 8;(86).
    doi: 10.3791/51076pmc: PMC4165283pubmed: 24747842google scholar: lookup
  19. Tessier L, Bienzle D, Williams LB, Koch TG. Phenotypic and immunomodulatory properties of equine cord blood-derived mesenchymal stromal cells.. PLoS One 2015;10(4):e0122954.
  20. Co C, Vickaryous MK, Koch TG. Membrane culture and reduced oxygen tension enhances cartilage matrix formation from equine cord blood mesenchymal stromal cells in vitro.. Osteoarthritis Cartilage 2014 Mar;22(3):472-80.
    doi: 10.1016/j.joca.2013.12.021pubmed: 24418676google scholar: lookup
  21. Leone L, Raffa S, Vetrano M, Ranieri D, Malisan F, Scrofani C, Vulpiani MC, Ferretti A, Torrisi MR, Visco V. Extracorporeal Shock Wave Treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs).. Oncotarget 2016 Feb 9;7(6):6410-23.
    doi: 10.18632/oncotarget.7064pmc: PMC4872723pubmed: 26843618google scholar: lookup
  22. Tay S, Hughey JJ, Lee TK, Lipniacki T, Quake SR, Covert MW. Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing.. Nature 2010 Jul 8;466(7303):267-71.
    doi: 10.1038/nature09145pmc: PMC3105528pubmed: 20581820google scholar: lookup
  23. Heneidi S, Simerman AA, Keller E, Singh P, Li X, Dumesic DA, Chazenbalk G. Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue.. PLoS One 2013;8(6):e64752.
  24. Chen KH, Hsiao HY, Glenn Wallace C, Lin KC, Li YC, Huang TH, Huang CR, Chen YL, Luo CW, Lee FY, Yip HK. Combined Adipose-Derived Mesenchymal Stem Cells and Low-Energy Extracorporeal Shock Wave Therapy Protect the Brain From Brain Death-Induced Injury in Rat.. J Neuropathol Exp Neurol 2019 Jan 1;78(1):65-77.
    doi: 10.1093/jnen/nly108pubmed: 30481326google scholar: lookup
  25. Sukubo NG, Tibalt E, Respizzi S, Locati M, d'Agostino MC. Effect of shock waves on macrophages: A possible role in tissue regeneration and remodeling.. Int J Surg 2015 Dec;24(Pt B):124-30.
    doi: 10.1016/j.ijsu.2015.07.719pubmed: 26291028google scholar: lookup
  26. Zhao Y, Wang J, Wang M, Sun P, Chen J, Jin X, Zhang H. Activation of bone marrow-derived mesenchymal stromal cells-a new mechanism of defocused low-energy shock wave in regenerative medicine.. Cytotherapy 2013 Dec;15(12):1449-57.
    doi: 10.1016/j.jcyt.2013.08.012pubmed: 24199590google scholar: lookup
  27. Rinella L, Marano F, Berta L, Bosco O, Fraccalvieri M, Fortunati N, Frairia R, Catalano MG. Extracorporeal shock waves modulate myofibroblast differentiation of adipose-derived stem cells.. Wound Repair Regen 2016 Mar;24(2):275-86.
    doi: 10.1111/wrr.12410pubmed: 26808471google scholar: lookup
  28. d'Agostino MC, Craig K, Tibalt E, Respizzi S. Shock wave as biological therapeutic tool: From mechanical stimulation to recovery and healing, through mechanotransduction.. Int J Surg 2015 Dec;24(Pt B):147-53.
    doi: 10.1016/j.ijsu.2015.11.030pubmed: 26612525google scholar: lookup
  29. Chen YJ, Kuo YR, Yang KD, Wang CJ, Sheen Chen SM, Huang HC, Yang YJ, Yi-Chih S, Wang FS. Activation of extracellular signal-regulated kinase (ERK) and p38 kinase in shock wave-promoted bone formation of segmental defect in rats.. Bone 2004 Mar;34(3):466-77.
    doi: 10.1016/j.bone.2003.11.013pubmed: 15003794google scholar: lookup
  30. Salcedo-Jimu00e9nez R, Koenig JB, Lee OJ, Gibson TWG, Madan P, Koch TG. Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells.. Front Vet Sci 2020;7:554306.
    doi: 10.1101/2020.01.10.901439pmc: PMC7746774pubmed: 33344521google scholar: lookup

Citations

This article has been cited 2 times.
  1. Jammes M, Contentin R, Cassu00e9 F, Galu00e9ra P. Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies.. Front Vet Sci 2023;10:1115774.
    doi: 10.3389/fvets.2023.1115774pubmed: 36846261google scholar: lookup
  2. Guo J, Hai H, Ma Y. Application of extracorporeal shock wave therapy in nervous system diseases: A review.. Front Neurol 2022;13:963849.
    doi: 10.3389/fneur.2022.963849pubmed: 36062022google scholar: lookup