Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
The research article focuses on exploring how Mesenchymal stem cells (MSCs) and insulin-like growth factor-I gene-enhanced Mesenchymal stem cells (AdIGF-MSCs) can contribute to the healing process of tendinitis, a common injury amongst athletes. The study indicates that MSCs and AdIGF-MSCs tend to improve tendon healing, thereby suggesting their potential use in tendinitis treatments.
Research Methodology
- The study involved creating artificial tendinitis lesions in equine flexor digitorum superficialis tendons (SDFT) using collagenase, as equine tendons closely simulate the characteristics of human tendons.
- The researchers then treated these tendons with either 10 x 10(6) MSCs or 10 x 10(6) AdIGF-MSCs. The control limbs were injected with 1 mL of phosphate-buffered saline (PBS) for comparison.
- Ultrasound examinations were conducted at different time intervals (t = 0, 2, 4, 6, 8 weeks) to observe the progress of tendon healing.
- Eight weeks post-treatment, the SDFTs were thoroughly examined for their mechanical strength, biochemical composition, and histologic characteristics to discern potential improvements.
Results and Findings
- Researchers found no variation in the expression of collagen types I and III, IGF-I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-13 (MMP-13), aggrecanase-1 (ADAMTS-4), and matrix metalloproteinase-3 (MMP-3) between the MSC treated and control tendons.
- However, both MSC and AdIGF-MSC injections significantly improved the histological scores of the tendon, suggesting better healing outcomes.
- These results provide evidence for the therapeutic potential of MSCs and AdIGF-MSCs in tendinitis treatment, whereby they may catalyze the healing process and improve tendon structure and function post-injury.
Conclusion
Overall, the study supports the application of Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced Mesenchymal stem cells for treating tendinitis. However, further studies may be required to understand the long-term implications and side effects of these advancements amidst different variable factors.
Cite This Article
Publication
Researcher Affiliations
- Comparative Orthopaedics Laboratory, Department of Clinical Sciences, C3-187 Veterinary Medical Center, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
MeSH Terms
- ADAM Proteins / metabolism
- ADAMTS4 Protein
- Animals
- Biomechanical Phenomena
- Cell- and Tissue-Based Therapy / methods
- Cell- and Tissue-Based Therapy / veterinary
- Collagen Type I / metabolism
- Collagen Type III / metabolism
- Extracellular Matrix Proteins / metabolism
- Female
- Genetic Therapy / methods
- Genetic Therapy / veterinary
- Glycoproteins / metabolism
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horse Diseases / therapy
- Horses
- Insulin-Like Growth Factor I / genetics
- Insulin-Like Growth Factor I / metabolism
- Male
- Matrilin Proteins
- Matrix Metalloproteinase 13 / metabolism
- Matrix Metalloproteinase 3 / metabolism
- Mesenchymal Stem Cell Transplantation / methods
- Mesenchymal Stem Cell Transplantation / veterinary
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / metabolism
- Procollagen N-Endopeptidase / metabolism
- Tendinopathy / metabolism
- Tendinopathy / therapy
- Tendinopathy / veterinary
- Tendons / diagnostic imaging
- Tendons / metabolism
- Tendons / pathology
- Ultrasonography
Citations
This article has been cited 80 times.- Ning C, Li P, Gao C, Fu L, Liao Z, Tian G, Yin H, Li M, Sui X, Yuan Z, Liu S, Guo Q. Recent advances in tendon tissue engineering strategy.. Front Bioeng Biotechnol 2023;11:1115312.
- Arnaud-Franco Á, Lara-Arias J, Marino-Martínez IA, Cienfuegos-Jiménez O, Barbosa-Quintana Á, Peña-Martínez VM. Effect of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Application in Achilles-Tendon Injury in an Animal Model.. Curr Issues Mol Biol 2022 Nov 22;44(12):5827-5838.
- Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK. TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing.. Stem Cell Res Ther 2022 Sep 16;13(1):477.
- Koch DW, Berglund AK, Messenger KM, Gilbertie JM, Ellis IM, Schnabel LV. Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells.. Front Vet Sci 2022;9:963759.
- Bowers K, Amelse L, Bow A, Newby S, MacDonald A, Sun X, Anderson D, Dhar M. Mesenchymal Stem Cell Use in Acute Tendon Injury: In Vitro Tenogenic Potential vs. In Vivo Dose Response.. Bioengineering (Basel) 2022 Aug 22;9(8).
- Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries.. Front Bioeng Biotechnol 2022;10:866195.
- 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.
- Hafeez MN, d'Avanzo N, Russo V, Di Marzio L, Cilurzo F, Paolino D, Fresta M, Barboni B, Santos HA, Celia C. Tendon Tissue Repair in Prospective of Drug Delivery, Regenerative Medicines, and Innovative Bioscaffolds.. Stem Cells Int 2021;2021:1488829.
- Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF. Evaluation of Autologous Protein Solution Injection for Treatment of Superficial Digital Flexor Tendonitis in an Equine Model.. Front Vet Sci 2021;8:697551.
- Meeremans M, Van de Walle GR, Van Vlierberghe S, De Schauwer C. The Lack of a Representative Tendinopathy Model Hampers Fundamental Mesenchymal Stem Cell Research.. Front Cell Dev Biol 2021;9:651164.
- Harman RM, Marx C, Van de Walle GR. Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy.. Front Cell Dev Biol 2021;9:654885.
- Bagge J, MacLeod JN, Berg LC. Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age.. Front Vet Sci 2020;7:602403.
- Citeroni MR, Ciardulli MC, Russo V, Della Porta G, Mauro A, El Khatib M, Di Mattia M, Galesso D, Barbera C, Forsyth NR, Maffulli N, Barboni B. In Vitro Innovation of Tendon Tissue Engineering Strategies.. Int J Mol Sci 2020 Sep 14;21(18).
- 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.
- Gugjoo MB, Hussain S, Amarpal, Shah RA, Dhama K. Mesenchymal Stem Cell-Mediated Immuno-Modulatory and Anti- Inflammatory Mechanisms in Immune and Allergic Disorders.. Recent Pat Inflamm Allergy Drug Discov 2020;14(1):3-14.
- Venkatesan JK, Rey-Rico A, Cucchiarini M. Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine.. Tissue Eng Regen Med 2019 Aug;16(4):345-355.
- 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.
- Grady ST, Watts AE, Thompson JA, Penedo MCT, Konganti K, Hinrichs K. Effect of intra-ovarian injection of mesenchymal stem cells in aged mares.. J Assist Reprod Genet 2019 Mar;36(3):543-556.
- Abat F, Alfredson H, Cucchiarini M, Madry H, Marmotti A, Mouton C, Oliveira JM, Pereira H, Peretti GM, Spang C, Stephen J, van Bergen CJA, de Girolamo L. Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II: treatment options.. J Exp Orthop 2018 Sep 24;5(1):38.
- Ahrberg AB, Horstmeier C, Berner D, Brehm W, Gittel C, Hillmann A, Josten C, Rossi G, Schubert S, Winter K, Burk J. Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model.. BMC Musculoskelet Disord 2018 Jul 18;19(1):230.
- Han SH, Kim HK, Ahn JH, Lee DH, Baek M, Ye G, Lee JM, Min K, Oh C, Lee S. A Protocol to Acquire the Degenerative Tenocyte from Humans.. J Vis Exp 2018 Jun 9;(136).
- 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.
- Guo X, Bai Y, Zhang L, Zhang B, Zagidullin N, Carvalho K, Du Z, Cai B. Cardiomyocyte differentiation of mesenchymal stem cells from bone marrow: new regulators and its implications.. Stem Cell Res Ther 2018 Feb 26;9(1):44.
- Pöschke A, Krähling B, Failing K, Staszyk C. Molecular Characteristics of the Equine Periodontal Ligament.. Front Vet Sci 2017;4:235.
- Andia I, Abate M. Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions.. Front Med 2018 Apr;12(2):139-152.
- Gong H, Wang X, Wang L, Liu Y, Wang J, Lv Q, Pang H, Zhang Q, Wang Z. Inhibition of IGF-1 receptor kinase blocks the differentiation into cardiomyocyte-like cells of BMSCs induced by IGF-1.. Mol Med Rep 2017 Jul;16(1):787-793.
- Sherman AB, Gilger BC, Berglund AK, Schnabel LV. Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro.. Stem Cell Res Ther 2017 May 25;8(1):120.
- Lang HM, Schnabel LV, Cassano JM, Fortier LA. Effect of needle diameter on the viability of equine bone marrow derived mesenchymal stem cells.. Vet Surg 2017 Jul;46(5):731-737.
- Hosseinikia R, Nikbakht MR, Moghaddam AA, Tajehmiri A, Hosseinikia M, Oubari F, Nikougoftar Zarif M, Pasdar Y, Mansouri K. Molecular and Cellular Interactions of Allogenic and Autologus Mesenchymal Stem Cells with Innate and Acquired Immunity and Their Role in Regenerative Medicine.. Int J Hematol Oncol Stem Cell Res 2017 Jan 1;11(1):63-77.
- Berglund AK, Schnabel LV. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.. Equine Vet J 2017 Jul;49(4):539-544.
- Scharf A, Holmes SP, Thoresen M, Mumaw J, Stumpf A, Peroni J. MRI-Based Assessment of Intralesional Delivery of Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Equine Tendonitis.. Stem Cells Int 2016;2016:8610964.
- White NA 2nd, Barrett JG. Magnetic Resonance Imaging-Guided Treatment of Equine Distal Interphalangeal Joint Collateral Ligaments: 2009-2014.. Front Vet Sci 2016;3:73.
- Burk J, Plenge A, Brehm W, Heller S, Pfeiffer B, Kasper C. Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching.. Stem Cells Int 2016;2016:7342379.
- Walden G, Liao X, Donell S, Raxworthy MJ, Riley GP, Saeed A. A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration.. Tissue Eng Part B Rev 2017 Feb;23(1):44-58.
- 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.
- Carr BJ, Canapp SO Jr, Mason DR, Cox C, Hess T. Canine Platelet-Rich Plasma Systems: A Prospective Analysis.. Front Vet Sci 2015;2:73.
- Sayegh ET, Sandy JD, Virk MS, Romeo AA, Wysocki RW, Galante JO, Trella KJ, Plaas A, Wang VM. Recent Scientific Advances Towards the Development of Tendon Healing Strategies.. Curr Tissue Eng 2015;4(2):128-143.
- 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.
- Lombana KG, Goodrich LR, Phillips JN, Kisiday JD, Ruple-Czerniak A, McIlwraith CW. An Investigation of Equine Mesenchymal Stem Cell Characteristics from Different Harvest Sites: More Similar Than Not.. Front Vet Sci 2015;2:67.
- Pezzanite LM, Fortier LA, Antczak DF, Cassano JM, Brosnahan MM, Miller D, Schnabel LV. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.. Stem Cell Res Ther 2015 Apr 12;6(1):54.
- Schmitt A, Rödel P, Anamur C, Seeliger C, Imhoff AB, Herbst E, Vogt S, van Griensven M, Winter G, Engert J. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.. PLoS One 2015;10(3):e0118937.
- Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system.. Nat Rev Rheumatol 2015 Apr;11(4):234-42.
- Schär MO, Diaz-Romero J, Kohl S, Zumstein MA, Nesic D. Platelet-rich concentrates differentially release growth factors and induce cell migration in vitro.. Clin Orthop Relat Res 2015 May;473(5):1635-43.
- Guevara-Alvarez A, Schmitt A, Russell RP, Imhoff AB, Buchmann S. Growth factor delivery vehicles for tendon injuries: Mesenchymal stem cells and Platelet Rich Plasma.. Muscles Ligaments Tendons J 2014 Jul;4(3):378-85.
- Docheva D, Müller SA, Majewski M, Evans CH. Biologics for tendon repair.. Adv Drug Deliv Rev 2015 Apr;84:222-39.
- Burk J, Gittel C, Heller S, Pfeiffer B, Paebst F, Ahrberg AB, Brehm W. Gene expression of tendon markers in mesenchymal stromal cells derived from different sources.. BMC Res Notes 2014 Nov 20;7:826.
- Ho JO, Sawadkar P, Mudera V. A review on the use of cell therapy in the treatment of tendon disease and injuries.. J Tissue Eng 2014;5:2041731414549678.
- MacLean S, Khan WS, Malik AA, Snow M, Anand S. Tendon regeneration and repair with stem cells.. Stem Cells Int 2012;2012:316281.
- Ozasa Y, Gingery A, Thoreson AR, An KN, Zhao C, Amadio PC. A comparative study of the effects of growth and differentiation factor 5 on muscle-derived stem cells and bone marrow stromal cells in an in vitro tendon healing model.. J Hand Surg Am 2014 Sep;39(9):1706-13.
- Schon LC, Gill N, Thorpe M, Davis J, Nadaud J, Kim J, Molligan J, Zhang Z. Efficacy of a mesenchymal stem cell loaded surgical mesh for tendon repair in rats.. J Transl Med 2014 May 2;12:110.
- Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA. Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro.. Stem Cell Res Ther 2014 Jan 24;5(1):13.
- Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine.. Exp Mol Med 2013 Nov 15;45(11):e54.
- Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.. PLoS One 2013;8(9):e75697.
- Xie L, Zhang N, Marsano A, Vunjak-Novakovic G, Zhang Y, Lopez MJ. In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.. Stem Cell Rev Rep 2013 Dec;9(6):858-72.
- Carvalho Ade M, Badial PR, Álvarez LE, Yamada AL, Borges AS, Deffune E, Hussni CA, Garcia Alves AL. Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial.. Stem Cell Res Ther 2013 Jul 22;4(4):85.
- Ruzzini L, Longo UG, Rizzello G, Denaro V. Stem cells and tendinopathy: state of the art from the basic science to clinic application.. Muscles Ligaments Tendons J 2012 Jul;2(3):235-8.
- Chaudhury S. Mesenchymal stem cell applications to tendon healing.. Muscles Ligaments Tendons J 2012 Jul;2(3):222-9.
- Tetta C, Consiglio AL, Bruno S, Tetta E, Gatti E, Dobreva M, Cremonesi F, Camussi G. The role of microvesicles derived from mesenchymal stem cells in tissue regeneration; a dream for tendon repair?. Muscles Ligaments Tendons J 2012 Jul;2(3):212-21.
- Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy.. Acta Pharmacol Sin 2013 Jun;34(6):747-54.
- Volk SW, Theoret C. Translating stem cell therapies: the role of companion animals in regenerative medicine.. Wound Repair Regen 2013 May-Jun;21(3):382-94.
- Seo MS, Park SB, Kim HS, Kang JG, Chae JS, Kang KS. Isolation and characterization of equine amniotic membrane-derived mesenchymal stem cells.. J Vet Sci 2013;14(2):151-9.
- Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, Shi Y. Concise review: mesenchymal stem cells and translational medicine: emerging issues.. Stem Cells Transl Med 2012 Jan;1(1):51-8.
- Spaas JH, Guest DJ, Van de Walle GR. Tendon regeneration in human and equine athletes: Ubi Sumus-Quo Vadimus (where are we and where are we going to)?. Sports Med 2012 Oct 1;42(10):871-90.
- Ranera B, Remacha AR, Álvarez-Arguedas S, Romero A, Vázquez FJ, Zaragoza P, Martín-Burriel I, Rodellar C. Effect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue.. BMC Vet Res 2012 Aug 22;8:142.
- Pelled G, Snedeker JG, Ben-Arav A, Rigozzi S, Zilberman Y, Kimelman-Bleich N, Gazit Z, Müller R, Gazit D. Smad8/BMP2-engineered mesenchymal stem cells induce accelerated recovery of the biomechanical properties of the Achilles tendon.. J Orthop Res 2012 Dec;30(12):1932-9.
- Young M. Stem cell applications in tendon disorders: a clinical perspective.. Stem Cells Int 2012;2012:637836.
- Majewski M, Porter RM, Betz OB, Betz VM, Clahsen H, Flückiger R, Evans CH. Improvement of tendon repair using muscle grafts transduced with TGF-β1 cDNA.. Eur Cell Mater 2012 Feb 16;23:94-101; discussion 101-2.
- Longo UG, Lamberti A, Petrillo S, Maffulli N, Denaro V. Scaffolds in tendon tissue engineering.. Stem Cells Int 2012;2012:517165.
- Mensing N, Gasse H, Hambruch N, Haeger JD, Pfarrer C, Staszyk C. Isolation and characterization of multipotent mesenchymal stromal cells from the gingiva and the periodontal ligament of the horse.. BMC Vet Res 2011 Aug 2;7:42.
- Granero-Moltó F, Myers TJ, Weis JA, Longobardi L, Li T, Yan Y, Case N, Rubin J, Spagnoli A. Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects.. Stem Cells 2011 Oct;29(10):1537-48.
- Schwarz C, Leicht U, Drosse I, Ulrich V, Luibl V, Schieker M, Röcken M. Characterization of adipose-derived equine and canine mesenchymal stem cells after incubation in agarose-hydrogel.. Vet Res Commun 2011 Dec;35(8):487-99.
- Chamberlain CS, Leiferman EM, Frisch KE, Wang S, Yang X, Brickson SL, Vanderby R. The influence of interleukin-4 on ligament healing.. Wound Repair Regen 2011 May-Jun;19(3):426-35.
- Torricelli P, Fini M, Filardo G, Tschon M, Pischedda M, Pacorini A, Kon E, Giardino R. Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses.. Int Orthop 2011 Oct;35(10):1569-76.
- Fortier LA, Travis AJ. Stem cells in veterinary medicine.. Stem Cell Res Ther 2011 Feb 23;2(1):9.
- Watts AE, Yeager AE, Kopyov OV, Nixon AJ. Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.. Stem Cell Res Ther 2011 Jan 27;2(1):4.
- Myers TJ, Granero-Molto F, Longobardi L, Li T, Yan Y, Spagnoli A. Mesenchymal stem cells at the intersection of cell and gene therapy.. Expert Opin Biol Ther 2010 Dec;10(12):1663-79.
- Morizaki Y, Zhao C, An KN, Amadio PC. The effects of platelet-rich plasma on bone marrow stromal cell transplants for tendon healing in vitro.. J Hand Surg Am 2010 Nov;35(11):1833-41.
- Hodgkinson CP, Gomez JA, Mirotsou M, Dzau VJ. Genetic engineering of mesenchymal stem cells and its application in human disease therapy.. Hum Gene Ther 2010 Nov;21(11):1513-26.
- Murray SJ, Santangelo KS, Bertone AL. Evaluation of early cellular influences of bone morphogenetic proteins 12 and 2 on equine superficial digital flexor tenocytes and bone marrow-derived mesenchymal stem cells in vitro.. Am J Vet Res 2010 Jan;71(1):103-14.
- Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair.. Tissue Eng Part B Rev 2010 Feb;16(1):105-15.