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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.
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Publication Date: 2019-12-18 PubMed ID: 31852535PubMed Central: PMC6921487DOI: 10.1186/s13287-019-1469-5Google Scholar: Lookup
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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

Stem cell research & therapy
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.

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