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Stem cell research & therapy2019; 10(1); 394; doi: 10.1186/s13287-019-1469-5

Microvesicles isolated from 5-azacytidine-and-resveratrol-treated mesenchymal stem cells for the treatment of suspensory ligament injury in horse-a case report.

Abstract: In athlete horses, suspensory ligament (SL) injuries are the most common cause of lameness. Healing of SL injury is still problematic, and even proper rehabilitation and pharmacological therapy do not guarantee returning to the initial performance level. In our previous studies, we have shown that a combination of 5-azacytidine (AZA) and resveratrol (RES) exerts beneficial, rejuvenating effects on metabolic syndrome derived adipose-derived stem cells (ASCs). Thus, in the presented research, we investigate whether not only rejuvenated ASC but also microvesicles (MVsAZA/RES) secreted by them possess enhanced regenerative properties in SL injury. In the presented study, a 6-year-old Dutch Warmblood gelding, working in jumping, was diagnosed with SL injury using ultrasonography, Doppler, real-time elastography and thermography. As a therapeutic strategy, the affected animal was treated with extracellular microvesicles derived from ASC treated with the combination of 5-azacytydine (AZA) and resveratrol (RES) (MVsAZA/RES). RESULTS: First, anti-apoptotic effects of MVsAZA/RES were tested in co-culture with metabolic syndrome derived ASC. The proliferation of cells and expression of pro-apoptotic genes were investigated. Then, MVsAZA/RES were injected directly into the injured SL of the Dutch Warmblood gelding. In vitro assays revealed that MVsAZA/RES enhance the proliferation of ASC and exert an anti-apoptotic effect. In the affected horse, the application of MVsAZA/RES resulted in increased lesion filling and improvement of angiogenesis and elasticity in injured tissue. As MVsAZA/RES mimic several of the biological actions exerted by ASC, they have become an alternative for stem cell-based therapies and can be effectively applied for the treatment of SL injury in horses.
Publication Date: 2019-12-18 PubMed ID: 31852535PubMed Central: PMC6921487DOI: 10.1186/s13287-019-1469-5Google Scholar: Lookup
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  • Case Reports
  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the use of microvesicles derived from adipose-derived stem cells (ASC), treated with 5-azacytydine and resveratrol, in healing suspensory ligament injuries in horses, which are a common cause of lameness. The study concluded that these microvesicles could effectively enhance cell proliferation, exert anti-apoptotic effects, improve lesion filling, and boost angiogenesis and elasticity in injured equine tissue.

Introduction

  • The study focuses on the treatment of suspensory ligament (SL) injuries in athlete horses, which often lead to lameness and do not necessarily heal even with proper rehabilitation and pharmacological therapy.
  • Earlier research had indicated rejuvenating effects on adipose-derived stem cells (ASCs) when treated with a combination of 5-azacytidine (AZA) and resveratrol (RES).
  • This research investigates whether microvesicles (MVs), which are secreted by rejuvenated ASCs, can possess enhanced regenerative properties when it comes to healing SL injuries.

Methodology

  • The study involves treating a 6-year-old Dutch Warmblood gelding diagnosed with an SL injury with extracellular microvesicles derived from ASCs treated with a combination of AZA and RES.
  • First, the anti-apoptotic effects of these MVs were tested in co-culture with ASCs derived from metabolic syndrome. The researchers monitored cell proliferation and pro-apoptotic gene expression.
  • These MVs were then directly injected into the horse’s injured SL.

Results

  • The in vitro tests showed that MVs enhance ASC proliferation and have an anti-apoptotic effect.
  • In the horse, the application of MVs led to increased filling of the lesion and improvement in angiogenesis (the formation of new blood vessels) and elasticity in the injured tissue.

Conclusion

  • The findings suggest that MVs, which mimic several of the biological actions of ASCs, could be a viable alternative for stem cell-based therapies.
  • These MVs can potentially be effectively applied for the treatment of SL injuries in horses, thus tackling a major cause of lameness in these animals and possibly improving their performance and quality of life.

Cite This Article

APA
Kornicka-Garbowska K, Pędziwiatr R, Woźniak P, Kucharczyk K, Marycz K. (2019). Microvesicles isolated from 5-azacytidine-and-resveratrol-treated mesenchymal stem cells for the treatment of suspensory ligament injury in horse-a case report. Stem Cell Res Ther, 10(1), 394. https://doi.org/10.1186/s13287-019-1469-5

Publication

ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 394

Researcher Affiliations

Kornicka-Garbowska, Katarzyna
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland.
  • International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
Pędziwiatr, Rafał
  • EQUI-VET Clinic for Horses, Stogniowice 55A, 32-100, Proszowice, Poland.
Woźniak, Paulina
  • International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
Kucharczyk, Katarzyna
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland.
  • International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland.
Marycz, Krzysztof
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland. krzysztofmarycz@interia.pl.
  • International Institute of Translational Medicine, Malin, Jesionowa 11, 55-114, Wisznia Mała, Poland. krzysztofmarycz@interia.pl.
  • Faculty of Veterinary Medicine, Equine Clinic-Equine Surgery, Justus-Liebig-University, 35392, Giessen, Germany. krzysztofmarycz@interia.pl.

MeSH Terms

  • Animals
  • Azacitidine / pharmacology
  • Cell-Derived Microparticles / metabolism
  • Cell-Derived Microparticles / transplantation
  • Elasticity Imaging Techniques
  • Horse Diseases / pathology
  • Horse Diseases / therapy
  • Horses
  • Ligaments / injuries
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Resveratrol / pharmacology
  • Ultrasonography
  • Wound Healing

Conflict of Interest Statement

The authors declare that they have no competing interests.

References

This article includes 48 references
  1. Kollias-Baker C. Therapeutics of musculoskeletal disease in the horse.. Vet Clin North Am Equine Pract 1999;15:589–602.
    doi: 10.1016/S0749-0739(17)30134-7pubmed: 10589469google scholar: lookup
  2. Kearns CF, McKeever KH, Abe T. Overview of horse body composition and muscle architecture: implications for performance.. Vet J 2002;164:224–234.
    doi: 10.1053/tvjl.2001.0702pubmed: 12505395google scholar: lookup
  3. Davidson EJ. Lameness evaluation of the athletic horse.. Vet Clin North Am Equine Pract 2018;34:181–191.
    doi: 10.1016/j.cveq.2018.04.013pubmed: 30007446google scholar: lookup
  4. Eddy AL, Van Hoogmoed LM, Snyder JR. The role of thermography in the management of equine lameness.. Vet J 2001;162:172–181.
    doi: 10.1053/tvjl.2001.0618pubmed: 11681868google scholar: lookup
  5. Tamura N, Nukada T, Kato T, Kuroda T, Kotoyori Y, Fukuda K. The use of sonoelastography to assess the recovery of stiffness after equine superficial digital flexor tendon injuries: a preliminary prospective longitudinal study of the healing process.. Equine Vet J 2017;49:590–595.
    doi: 10.1111/evj.12665pubmed: 28083881google scholar: lookup
  6. Lutter JD, Schneider RK, Sampson SN, Cary JA, Roberts GD, Vahl CI. Medical treatment of horses with deep digital flexor tendon injuries diagnosed with high-field-strength magnetic resonance imaging: 118 cases (2000–2010). J Am Vet Med Assoc 2015;247:1309–1318.
    doi: 10.2460/javma.247.11.1309pubmed: 26594815google scholar: lookup
  7. Clinical evaluation of intralesional injection of platelet-rich plasma for the treatment of proximal suspensory ligament desmitis in horses - ScienceDirect. [cited 2019 Apr 26]. Available from: https://www.sciencedirect.com/science/article/pii/S0737080614004729?via%3Dihub
  8. Thorpe CT, Clegg PD, Birch HL. A review of tendon injury: why is the equine superficial digital flexor tendon most at risk?. Equine Vet J 2010;42:174–180.
    doi: 10.2746/042516409X480395pubmed: 20156256google scholar: lookup
  9. Geburek F, Gaus M, van Schie HTM, Rohn K, Stadler PM. Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies – a randomized prospective controlled clinical trial.. BMC Vet Res 2016;12.
    pmc: PMC5015224pubmed: 27604193
  10. Beerts C, Suls M, Broeckx SY, Seys B, Vandenberghe A, Declercq J. Tenogenically induced allogeneic peripheral blood mesenchymal stem cells in allogeneic platelet-rich plasma: 2-year follow-up after tendon or ligament treatment in horses.. Front Vet Sci 2017;4.
    pmc: PMC5622984pubmed: 29018808
  11. Cislo-Pakuluk A, Marycz K. A promising tool in retina regeneration: current perspectives and challenges when using mesenchymal progenitor stem cells in veterinary and human ophthalmological applications.. Stem Cell Rev 2017;13:598–602.
    doi: 10.1007/s12015-017-9750-4pmc: PMC5602072pubmed: 28643176google scholar: lookup
  12. Akyurekli C, Le Y, Richardson RB, Fergusson D, Tay J, Allan DS. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles.. Stem Cell Rev and Rep 2015;11:150–160.
    doi: 10.1007/s12015-014-9545-9pubmed: 25091427google scholar: lookup
  13. Wei X, Yang X, Han Z, Qu F, Shao L, Shi Y. Mesenchymal stem cells: a new trend for cell therapy.. Acta Pharmacol Sin 2013;34:747–754.
    doi: 10.1038/aps.2013.50pmc: PMC4002895pubmed: 23736003google scholar: lookup
  14. Fiore EJ, Mazzolini G, Aquino JB. Mesenchymal stem/stromal cells in liver fibrosis: recent findings, old/new caveats and future perspectives.. Stem Cell Rev and Rep 2015;11:586–597.
    doi: 10.1007/s12015-015-9585-9pubmed: 25820543google scholar: lookup
  15. Lindroos B, Suuronen R, Miettinen S. The potential of adipose stem cells in regenerative medicine.. Stem Cell Rev 2011;7:269–291.
    doi: 10.1007/s12015-010-9193-7pubmed: 20853072google scholar: lookup
  16. Natsu K, Ochi M, Mochizuki Y, Hachisuka H, Yanada S, Yasunaga Y. Allogeneic bone marrow-derived mesenchymal stromal cells promote the regeneration of injured skeletal muscle without differentiation into myofibers.. Tissue Eng 2004;10:1093–1112.
    doi: 10.1089/ten.2004.10.1093pubmed: 15363167google scholar: lookup
  17. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.. Stem Cells 2007;25:2739–2749.
    doi: 10.1634/stemcells.2007-0197pubmed: 17656645google scholar: lookup
  18. Ståhl A, Johansson K, Mossberg M, Kahn R, Karpman D. Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases.. Pediatr Nephrol 2019;34:11–30.
    doi: 10.1007/s00467-017-3816-zpmc: PMC6244861pubmed: 29181712google scholar: lookup
  19. Panfoli I, Santucci L, Bruschi M, Petretto A, Calzia D, Ramenghi LA. Microvesicles as promising biological tools for diagnosis and therapy.. Expert Rev Proteomics 2018;15:801–808.
    doi: 10.1080/14789450.2018.1528149pubmed: 30253662google scholar: lookup
  20. Pashoutan Sarvar D, Shamsasenjan K, Akbarzadehlaleh P. Mesenchymal stem cell-derived exosomes: new opportunity in cell-free therapy.. Adv Pharm Bull 2016;6:293–299.
    doi: 10.15171/apb.2016.041pmc: PMC5071792pubmed: 27766213google scholar: lookup
  21. Choi W, Kwon S-J, Jin HJ, Jeong SY, Choi SJ, Oh W. Optimization of culture conditions for rapid clinical-scale expansion of human umbilical cord blood-derived mesenchymal stem cells.. Clin Transl Med 2017;6:38.
    doi: 10.1186/s40169-017-0168-zpmc: PMC5634990pubmed: 29019171google scholar: lookup
  22. Haraszti RA, Miller R, Stoppato M, Sere YY, Coles A, Didiot M-C. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity.. Mol Ther 2018;26:2838–2847.
    doi: 10.1016/j.ymthe.2018.09.015pmc: PMC6277553pubmed: 30341012google scholar: lookup
  23. Kornicka K, Marycz K, Tomaszewski KA, Marędziak M, Śmieszek A. The effect of age on osteogenic and adipogenic differentiation potential of human adipose derived stromal stem cells (hASCs) and the impact of stress factors in the course of the differentiation process.. Oxid Med Cell Longev 2015;2015:309169.
    doi: 10.1155/2015/309169pmc: PMC4515302pubmed: 26246868google scholar: lookup
  24. Nawrocka D, Kornicka K, Szydlarska J, Marycz K. Basic fibroblast growth factor inhibits apoptosis and promotes proliferation of adipose-derived mesenchymal stromal cells isolated from patients with type 2 diabetes by reducing cellular oxidative stress. Oxidative Medicine and Cellular Longevity. 2017 [cited 2017 Jul 27]. Available from: https://www.hindawi.com/journals/omcl/2017/3027109/ref/
    pmc: PMC5267085pubmed: 28168007
  25. Jumabay M, Moon JH, Yeerna H, Boström KI. Effect of diabetes mellitus on adipocyte-derived stem cells in rat.. J Cell Physiol 2015;230:2821–2828.
    doi: 10.1002/jcp.25012pmc: PMC4516692pubmed: 25854185google scholar: lookup
  26. Marycz K, Kornicka K, Marędziak M, Golonka P, Nicpoń J. Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.. J Cell Mol Med 2016;20:2384–2404.
    doi: 10.1111/jcmm.12932pmc: PMC5134411pubmed: 27629697google scholar: lookup
  27. Kornicka K, Szłapka-Kosarzewska J, Śmieszek A, Marycz K. 5-Azacytydine and resveratrol reverse senescence and ageing of adipose stem cells via modulation of mitochondrial dynamics and autophagy.. J Cell Mol Med 2018.
    pmc: PMC6307768pubmed: 30370650
  28. Kornicka K, Śmieszek A, Węgrzyn AS, Röcken M, Marycz K. Immunomodulatory properties of adipose-derived stem cells treated with 5-azacytydine and resveratrol on peripheral blood mononuclear cells and macrophages in metabolic syndrome animals.. J Clin Med 2018;7:383.
    doi: 10.3390/jcm7110383pmc: PMC6262510pubmed: 30356025google scholar: lookup
  29. Marycz K, Kornicka K, Irwin-Houston JM, Weiss C. Combination of resveratrol and 5-azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells.. J Cell Mol Med 2018;22:4771–4793.
    doi: 10.1111/jcmm.13731pmc: PMC6156237pubmed: 29999247google scholar: lookup
  30. Cha JM, Shin EK, Sung JH, Moon GJ, Kim EH, Cho YH. Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells.. Sci Rep 2018;8.
    pmc: PMC5775399pubmed: 29352188
  31. Nakamura Y, Miyaki S, Ishitobi H, Matsuyama S, Nakasa T, Kamei N. Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration.. FEBS Lett 2015;589:1257–1265.
    doi: 10.1016/j.febslet.2015.03.031pubmed: 25862500google scholar: lookup
  32. Marycz K, Kornicka K, Basinska K, Czyrek A. Equine metabolic syndrome affects viability, senescence, and stress factors of equine adipose-derived mesenchymal stromal stem cells: new insight into EqASCs isolated from EMS horses in the context of their aging. Oxidative Medicine and Cellular Longevity. 2016;2016:1–17.
    pmc: PMC4670679pubmed: 26682006
  33. Szatanek R, Baran J, Siedlar M, Baj-Krzyworzeka M. Isolation of extracellular vesicles: determining the correct approach (review). Int J Mol Med 2015;36:11–17.
    doi: 10.3892/ijmm.2015.2194pmc: PMC4494580pubmed: 25902369google scholar: lookup
  34. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987;162:156–159.
    doi: 10.1016/0003-2697(87)90021-2pubmed: 2440339google scholar: lookup
  35. Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies.. Mech Ageing Dev 2008;129:163–173.
    doi: 10.1016/j.mad.2007.12.002pubmed: 18241911google scholar: lookup
  36. Kornicka K, Houston J, Marycz K. Dysfunction of mesenchymal stem cells isolated from metabolic syndrome and type 2 diabetic patients as result of oxidative stress and autophagy may limit their potential therapeutic use.. Stem Cell Rev and Rep 2018:1–9.
    pmc: PMC5960487pubmed: 29611042
  37. Bourebaba Lynda, Röcken Michael, Marycz Krzysztof. Osteochondritis dissecans (OCD) in Horses – Molecular Background of its Pathogenesis and Perspectives for Progenitor Stem Cell Therapy.. Stem Cell Reviews and Reports 2019;15(3):374–390.
    doi: 10.1007/s12015-019-09875-6pmc: PMC6534522pubmed: 30796679google scholar: lookup
  38. Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and selective mitophagy ameliorate chondrogenic differentiation potential in adipose stem cells of equine metabolic syndrome: new findings in the field of progenitor cells differentiation.. Oxid Med Cell Longev 2016.
    pmc: PMC5178365pubmed: 28053691
  39. Kornicka K, Babiarczuk B, Krzak J, Marycz K. The effect of a sol–gel derived silica coating doped with vitamin E on oxidative stress and senescence of human adipose-derived mesenchymal stem cells (AMSCs). RSC Adv 2016;6:29524–29537.
    doi: 10.1039/C6RA00029Kgoogle scholar: lookup
  40. Nawrocka Daria, Kornicka Katarzyna, Śmieszek Agnieszka, Marycz Krzysztof. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses.. Marine Drugs 2017;15(8):237.
    doi: 10.3390/md15080237pmc: PMC5577592pubmed: 28771165google scholar: lookup
  41. Marycz Krzysztof, Michalak Izabela, Kocherova Ievgeniia, Marędziak Monika, Weiss Christine. The Cladophora glomerata Enriched by Biosorption Process in Cr(III) Improves Viability, and Reduces Oxidative Stress and Apoptosis in Equine Metabolic Syndrome Derived Adipose Mesenchymal Stromal Stem Cells (ASCs) and Their Extracellular Vesicles (MV’s). Marine Drugs 2017;15(12):385.
    doi: 10.3390/md15120385pmc: PMC5742845pubmed: 29292726google scholar: lookup
  42. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. - PubMed - NCBI. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19389847
    pmc: PMC2676194pubmed: 19389847
  43. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. - PubMed - NCBI. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22431999
    pmc: PMC3303802pubmed: 22431999
  44. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. - PubMed - NCBI. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21324974
    pubmed: 21324974
  45. Herrera MB, Fonsato V, Gatti S, Deregibus MC, Sordi A, Cantarella D. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats.. J Cell Mol Med 2010;14:1605–1618.
  46. Anabolic effects of acellular bone marrow, platelet rich plasma, and serum on equine suspensory ligament fibroblasts in vitro. - PubMed - NCBI. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16594543
    pubmed: 16594543
  47. Tenogenically induced allogeneic mesenchymal stem cells for the treatment of proximal suspensory ligament desmitis in a horse. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672201/
    pmc: PMC4672201pubmed: 26664976
  48. Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs. - PubMed - NCBI. [cited 2019 Apr 26]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15304271/
    pubmed: 15304271

Citations

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  1. González E, Falcón-Pérez JM. Expanding Horizons: Next-Generation and Interdisciplinary Advances in the Applications of Extracellular Vesicles. J Extracell Biol 2025 Dec;4(12):e70101.
    doi: 10.1002/jex2.70101pubmed: 41404187google scholar: lookup
  2. Gad WA, Ibrahim S, Nagdy H, Elsawy BSM, Aboelsoued D, Abdel-Ghany HSM, Abdel-Wareth AAA, Abd El-Razik KA, Mahmoud KGM, Soliman WTM, Taqi MO. Bridging biology and therapy: translational advances of extracellular vesicles in veterinary clinical practice. Vet Res Commun 2025 Nov 17;50(1):42.
    doi: 10.1007/s11259-025-10917-3pubmed: 41247562google scholar: lookup
  3. Milczek-Haduch D, Żmigrodzka M, Witkowska-Piłaszewicz O. Extracellular Vesicles in Sport Horses: Potential Biomarkers and Modulators of Exercise Adaptation and Therapeutics. Int J Mol Sci 2025 May 3;26(9).
    doi: 10.3390/ijms26094359pubmed: 40362597google scholar: lookup
  4. Guerra-Gomes M, Ferreira-Baptista C, Barros J, Alves-Pimenta S, Gomes P, Colaço B. Exploring the Potential of Non-Cellular Orthobiologic Products in Regenerative Therapies for Stifle Joint Diseases in Companion Animals. Animals (Basel) 2025 Feb 18;15(4).
    doi: 10.3390/ani15040589pubmed: 40003071google scholar: lookup
  5. Russo M, Lepre CC, Conza G, Tangredi N, D'Amico G, Braile A, Moretti A, Tarantino U, Gimigliano F, D'Amico M, Trotta MC, Toro G. New Insights on the miRNA Role in Diabetic Tendinopathy: Adipose-Derived Mesenchymal Stem Cell Conditioned Medium as a Potential Innovative Epigenetic-Based Therapy for Tendon Healing. Biomolecules 2025 Feb 11;15(2).
    doi: 10.3390/biom15020264pubmed: 40001567google scholar: lookup
  6. Guest DJ, Birch HL, Thorpe CT. A review of the equine suspensory ligament: Injury prone yet understudied. Equine Vet J 2025 Sep;57(5):1167-1182.
    doi: 10.1111/evj.14447pubmed: 39604165google scholar: lookup
  7. Younesi FS, Hinz B. The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair?. Int J Mol Sci 2024 Aug 9;25(16).
    doi: 10.3390/ijms25168712pubmed: 39201399google scholar: lookup
  8. Lanci A, Iacono E, Merlo B. Therapeutic Application of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Domestic Animals. Animals (Basel) 2024 Jul 24;14(15).
    doi: 10.3390/ani14152147pubmed: 39123673google scholar: lookup
  9. Xiong Y, Lou P, Xu C, Han B, Liu J, Gao J. Emerging role of extracellular vesicles in veterinary practice: novel opportunities and potential challenges. Front Vet Sci 2024;11:1335107.
    doi: 10.3389/fvets.2024.1335107pubmed: 38332755google scholar: lookup
  10. Caliani Carrera AL, Minto BW, Malard P, Brunel HDSS. The Role of Mesenchymal Stem Cell Secretome (Extracellular Microvesicles and Exosomes) in Animals' Musculoskeletal and Neurologic-Related Disorders. Vet Med Int 2023;2023:8819506.
    doi: 10.1155/2023/8819506pubmed: 38023428google scholar: lookup
  11. El-Husseiny HM, Mady EA, Helal MAY, Tanaka R. The Pivotal Role of Stem Cells in Veterinary Regenerative Medicine and Tissue Engineering. Vet Sci 2022 Nov 21;9(11).
    doi: 10.3390/vetsci9110648pubmed: 36423096google scholar: lookup
  12. Moccia V, Sammarco A, Cavicchioli L, Castagnaro M, Bongiovanni L, Zappulli V. Extracellular Vesicles in Veterinary Medicine. Animals (Basel) 2022 Oct 10;12(19).
    doi: 10.3390/ani12192716pubmed: 36230457google scholar: lookup
  13. Lui PPY, Leung YT. Practical Considerations for Translating Mesenchymal Stromal Cell-Derived Extracellular Vesicles from Bench to Bed. Pharmaceutics 2022 Aug 12;14(8).
    doi: 10.3390/pharmaceutics14081684pubmed: 36015310google scholar: lookup
  14. Trachsel DS, Stage HJ, Rausch S, Trappe S, Söllig K, Sponder G, Merle R, Aschenbach JR, Gehlen H. Comparison of Sources and Methods for the Isolation of Equine Adipose Tissue-Derived Stromal/Stem Cells and Preliminary Results on Their Reaction to Incubation with 5-Azacytidine. Animals (Basel) 2022 Aug 11;12(16).
    doi: 10.3390/ani12162049pubmed: 36009640google scholar: lookup
  15. Tracy EP, Stielberg V, Rowe G, Benson D, Nunes SS, Hoying JB, Murfee WL, LeBlanc AJ. State of the field: cellular and exosomal therapeutic approaches in vascular regeneration. Am J Physiol Heart Circ Physiol 2022 Apr 1;322(4):H647-H680.
    doi: 10.1152/ajpheart.00674.2021pubmed: 35179976google scholar: lookup
  16. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pubmed: 33477808google scholar: lookup
  17. Weiss C, Kornicka-Grabowska K, Mularczyk M, Siwinska N, Marycz K. Extracellular Microvesicles (MV's) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells. Stem Cell Rev Rep 2020 Dec;16(6):1343-1355.
    doi: 10.1007/s12015-020-10035-4pubmed: 32880856google scholar: lookup
  18. Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options. Front Vet Sci 2020;7:278.
    doi: 10.3389/fvets.2020.00278pubmed: 32656249google scholar: lookup