Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.
Abstract: Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required. Objective: We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries. Methods: In vivo experimental study. Methods: Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h. Results: Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse. Conclusions: Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.
© 2013 EVJ Ltd.
Publication Date: 2013-04-09 PubMed ID: 23574488DOI: 10.1111/evj.12063Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
- Clinical Study
- Deep Digital Flexor Tendon
- Disease Treatment
- Equine Diseases
- Equine Health
- Equine Science
- Experimental Methods
- Horses
- In Vivo
- Injury
- Intra-Articular Injection
- Intravenous Administration
- Mesenchymal Cells
- Scintigraphy
- Stem Cells
- Superficial Digital Flexor Tendon
- Tendons
- Veterinary Care
- Veterinary Medicine
- Veterinary Research
Summary
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This research article investigates the distribution and persistence of bone marrow-derived mesenchymal stem cells (MSCs) in tendon lesions in horses. The team compared different techniques for the injection of MSCs and hypothesized that vascular perfusion of the lower limb would lead to a higher concentration of MSCs in acute injuries. While the intralesional (i.l.) injection technique saw a higher initial uptake, its persistence decreased at similar rates across all methods. A time-dependent accumulation was found with intra-arterial regional limb perfusion (i.a. RLP).
Objective and Hypothesis
- The article’s objective is to study the efficiency of the different methods of injecting mesenchymal stem cells (MSCs) into tendon lesions, particularly comparing intratendinous injection and limb perfusion in horses.
- The hypothesis was that vascular perfusion of the distal limb in horses with MSCs would result in a more concentrated distribution of MSCs in acute tendon injuries.
Methodology
- An experimental study was conducted in vivo, meaning within the living body of the horse.
- Lesions were surgically induced in the superficial digital flexor tendons of the forelimbs of 8 horses. Three or 10 days after the lesion induction, MSCs labelled with technetium-99 hexamethyl propylene amine oxime were injected into the horses in three ways: intravenous or intra-arterial regional limb perfusion at the level of the distal antebrachium, and intratendinous injection.
- The persistence and distribution of MSCs within the forelimb and tendon lesions were assessed using scintigraphy, a diagnostic test that allows for imaging of the inside of the body, for 24 hours following the procedures.
Results
- Higher initial uptake was observed with direct injections into the lesion as compared to regional limb perfusion (RLP), however, the persistence of MSCs declined at similar rates across all three techniques.
- The intra-arterial RLP technique resulted in more evenly distributed MSCs and a higher uptake at the lesion site compared to intravenous RLP.
- When the limb was perfused intra-arterially on the tenth day, a greater accumulation of MSCs in the lesion was observed than when perfused on the third day.
- However, arterial thrombosis (blood clots) occurred with both intra-arterial and intravenous RLP, leading to clinical complications in one of the horses in the experiment.
Conclusion
- The article concludes that while RLP showed lower uptake than direct lesion injection, the two techniques exhibited similar persistence of MSCs at the lesion site.
- The scientists identified a time-dependent accumulation of MSCs with the use of intra-arterial RLP, although complications occurred such as arterial blood clots.
- It was concluded that the intra-arterial RLP method has advantages over the intravenous RLP method in terms of distribution and uptake, but due to the risk of arterial thrombosis, it cannot currently be suggested for clinical use.
Cite This Article
APA
Sole A, Spriet M, Padgett KA, Vaughan B, Galuppo LD, Borjesson DL, Wisner ER, Vidal MA.
(2013).
Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.
Equine Vet J, 45(6), 726-731.
https://doi.org/10.1111/evj.12063 Publication
Researcher Affiliations
- Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, USA.
MeSH Terms
- Animals
- Female
- Forelimb
- Horse Diseases / diagnostic imaging
- Horse Diseases / therapy
- Horses
- Macrophages / metabolism
- Male
- Mesenchymal Stem Cell Transplantation / veterinary
- Radionuclide Imaging / veterinary
- Technetium Tc 99m Exametazime / pharmacology
- Tendon Injuries / diagnostic imaging
- Tendon Injuries / therapy
- Ultrasonography
Citations
This article has been cited 19 times.- Maeda S, Kawamura T, Sasaki M, Shimamura K, Shibuya T, Harada A, Honmou O, Sawa Y, Miyagawa S. Intravenous infusion of bone marrow-derived mesenchymal stem cells improves tissue perfusion in a rat hindlimb ischemia model.. Sci Rep 2022 Oct 10;12(1):16986.
- Li C, Qin H, Zeng L, Hu Z, Chen C. Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis.. Stem Cell Res Ther 2022 Sep 5;13(1):452.
- Roth SP, Burk J, Brehm W, Troillet A. MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms.. Front Bioeng Biotechnol 2022;10:855095.
- Mund SJK, MacPhee DJ, Campbell J, Honaramooz A, Wobeser B, Barber SM. Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses.. Cells 2021 Nov 1;10(11).
- Aldrich ED, Cui X, Murphy CA, Lim KS, Hooper GJ, McIlwraith CW, Woodfield TBF. Allogeneic mesenchymal stromal cells for cartilage regeneration: A review of in vitro evaluation, clinical experience, and translational opportunities.. Stem Cells Transl Med 2021 Nov;10(11):1500-1515.
- Pluim M, Martens A, Vanderperren K, van Weeren R, Oosterlinck M, Dewulf J, Kichouh M, Van Thielen B, Koene MHW, Luciani A, Plancke L, Delesalle C. High-Power Laser Therapy Improves Healing of the Equine Suspensory Branch in a Standardized Lesion Model.. Front Vet Sci 2020;7:600.
- Ribitsch I, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton LC, Connolly DJ, van Steenbeek FG, Dudhia J, Penning LC. Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do.. Front Bioeng Biotechnol 2020;8:972.
- Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options.. Front Vet Sci 2020;7:278.
- Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges.. Stem Cell Res Ther 2019 Jun 18;10(1):181.
- Freedman BR, Mooney DJ. Biomaterials to Mimic and Heal Connective Tissues.. Adv Mater 2019 May;31(19):e1806695.
- Barberini DJ, Aleman M, Aristizabal F, Spriet M, Clark KC, Walker NJ, Galuppo LD, Amorim RM, Woolard KD, Borjesson DL. Safety and tracking of intrathecal allogeneic mesenchymal stem cell transplantation in healthy and diseased horses.. Stem Cell Res Ther 2018 Apr 10;9(1):96.
- Barboni B, Russo V, Berardinelli P, Mauro A, Valbonetti L, Sanyal H, Canciello A, Greco L, Muttini A, Gatta V, Stuppia L, Mattioli M. Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance.. Cell Transplant 2018 Jan;27(1):93-116.
- Kuemmerle JM, Theiss F, Okoniewski MJ, Weber FA, Hemmi S, Mirsaidi A, Richards PJ, Cinelli P. Identification of Novel Equine (Equus caballus) Tendon Markers Using RNA Sequencing.. Genes (Basel) 2016 Nov 10;7(11).
- Owens SD, Kol A, Walker NJ, Borjesson DL. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses.. Stem Cells Int 2016;2016:5830103.
- Berner D, Brehm W, Gerlach K, Gittel C, Offhaus J, Paebst F, Scharner D, Burk J. Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging.. Stem Cells Int 2016;2016:1207190.
- Geburek F, Mundle K, Conrad S, Hellige M, Walliser U, van Schie HT, van Weeren R, Skutella T, Stadler PM. Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study.. Stem Cell Res Ther 2016 Feb 1;7:21.
- Lui PP. Stem cell technology for tendon regeneration: current status, challenges, and future research directions.. Stem Cells Cloning 2015;8:163-74.
- Dudhia J, Becerra P, Valdés MA, Neves F, Hartman NG, Smith RK. In Vivo Imaging and Tracking of Technetium-99m Labeled Bone Marrow Mesenchymal Stem Cells in Equine Tendinopathy.. J Vis Exp 2015 Dec 9;(106):e52748.
- Vu Q, Xie K, Eckert M, Zhao W, Cramer SC. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke.. Neurology 2014 Apr 8;82(14):1277-86.
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