Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.
Abstract: Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase. Methods: Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacarpal region of the superficial digital flexor tendon (SDFT) of eight female adult Thoroughbred or Thoroughbred cross horses. Tendon lesions were treated one week later with intra-lesional injection of male derived fdESCs in media or media alone. Therapy was blinded and randomized. Serial ultrasound examinations were performed and final analysis at eight weeks included magnetic resonance imaging (MRI), biochemical assays (total DNA, glycosaminoglycan, collagen), gene expression (TNC, TNMD, SCX, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3, MMP13, 18S) and histology. Differences between groups were assessed with Wilcoxon's rank sum test. Results: Cell survival was demonstrated via the presence of the SRY gene in fdESC treated, but not control treated, female SDFT at the end of the trial. There were no differences in tendon matrix specific gene expression or total proteoglycan, collagen or DNA of tendon lesions between groups. Tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern were significantly improved on histologic sections and ultrasound in the fdESC treated tendons. Conclusions: Such profound structural effects lend further support to the notion that pluripotent stem cells can effect musculoskeletal regeneration, rather than repair, even without in vitro lineage specific differentiation. Further investigation into the safety of pluripotent cellular therapy as well as the mechanisms by which repair was improved seem warranted.
Publication Date: 2011-01-27 PubMed ID: 21272343PubMed Central: PMC3092144DOI: 10.1186/scrt45Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- 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.
The research explores the use of fetal derived embryonic-like stem cells to enhance the healing of tendon injuries in large animals, particularly horses. The research found that these stem cells offer considerable promise in regenerating rather than merely repairing damaged tendons.
Research Methodology
- The study applies a tendon injury model using collagenase gel-physical defect in adult Thoroughbred or Thoroughbred cross horses. The model created a controllable mid-metacarpal tendon injury in the superficial digital flexor tendon (SDFT).
- Seven days after inducing the injury, an intra-lesional injection of male-derived fetal embryonic-like stem cells (fdESC) suspended in a medium, denoted as the treatment, was administered in the tendon lesions.
- The study used a blinded and randomized therapy process to avoid any inadvertent bias.
- Regular ultrasound examinations were performed to monitor the progress in the healing of injuries. A final examination at eight weeks involved a range of tests including magnetic resonance imaging (MRI), gene expression tests, biochemical assays, and histology.
Research Findings
- The presence of the SRY gene in fdESC treated samples confirmed cell survival, which was absent in the control samples. However, no significant differences were found in the tendon matrix’s specific gene expression or proteoglycan, collagen, or DNA of tendon lesions between the treated and control groups.
- Significant improvements were noticed in tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern in the treated tendons both on histologic sections and through ultrasound imaging.
Conclusions and Implications
- The results of this study support the idea that pluripotent stem cells can facilitate musculoskeletal regeneration beyond mere repair, even without the need for in vitro lineage-specific differentiation.
- Given these promising findings, the research team recommends further investigations into the safety parameters of pluripotent cellular therapy and the exact mechanisms that brought about improved repair.
Cite This Article
APA
Watts AE, Yeager AE, Kopyov OV, Nixon AJ.
(2011).
Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.
Stem Cell Res Ther, 2(1), 4.
https://doi.org/10.1186/scrt45 Publication
Researcher Affiliations
- Department of Clinical Sciences, Comparative Orthopaedics Laboratory at Cornell University, Ithaca, NY, 14850 USA. ajn1@cornell.edu
MeSH Terms
- Animals
- Collagen / genetics
- Collagen / immunology
- Collagen / metabolism
- DNA / metabolism
- Disease Models, Animal
- Female
- Horse Diseases / diagnostic imaging
- Horse Diseases / pathology
- Horse Diseases / therapy
- Horses
- Magnetic Resonance Imaging
- Male
- Proteoglycans / genetics
- Proteoglycans / metabolism
- Regenerative Medicine
- Sex-Determining Region Y Protein / genetics
- Sex-Determining Region Y Protein / metabolism
- Stem Cell Transplantation / veterinary
- Stem Cells / cytology
- Tendon Injuries / diagnostic imaging
- Tendon Injuries / therapy
- Tendon Injuries / veterinary
- Ultrasonography
- Wound Healing
References
This article includes 54 references
- Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling.. J Musculoskelet Neuronal Interact 2006 Apr-Jun;6(2):181-90.
- Kader D, Saxena A, Movin T, Maffulli N. Achilles tendinopathy: some aspects of basic science and clinical management.. Br J Sports Med 2002 Aug;36(4):239-49.
- Jeffcott LB, Rossdale PD, Freestone J, Frank CJ, Towers-Clark PF. An assessment of wastage in thoroughbred racing from conception to 4 years of age.. Equine Vet J 1982 Jul;14(3):185-98.
- Rossdale PD, Hopes R, Digby NJ, offord K. Epidemiological study of wastage among racehorses 1982 and 1983.. Vet Rec 1985 Jan 19;116(3):66-9.
- Abate M, Silbernagel KG, Siljeholm C, Di Iorio A, De Amicis D, Salini V, Werner S, Paganelli R. Pathogenesis of tendinopathies: inflammation or degeneration?. Arthritis Res Ther 2009;11(3):235.
- Dowling BA, Dart AJ, Hodgson DR, Smith RK. Superficial digital flexor tendonitis in the horse.. Equine Vet J 2000 Sep;32(5):369-78.
- Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair.. J Bone Joint Surg Am 2005 Jan;87(1):187-202.
- McLauchlan GJ, Handoll HH. Interventions for treating acute and chronic Achilles tendinitis.. Cochrane Database Syst Rev 2001;(2):CD000232.
- Maffulli N, Longo UG, Loppini M, Denaro V. Current treatment options for tendinopathy.. Expert Opin Pharmacother 2010 Sep;11(13):2177-86.
- Jones ME, Mudera V, Brown RA, Cambrey AD, Grobbelaar AO, McGrouther DA. The early surface cell response to flexor tendon injury.. J Hand Surg Am 2003 Mar;28(2):221-30.
- Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE. Chondrogenic and adipogenic potential of microvascular pericytes.. Circulation 2004 Oct 12;110(15):2226-32.
- Clegg PD, Strassburg S, Smith RK. Cell phenotypic variation in normal and damaged tendons.. Int J Exp Pathol 2007 Aug;88(4):227-35.
- Woo SL, Hildebrand K, Watanabe N, Fenwick JA, Papageorgiou CD, Wang JH. Tissue engineering of ligament and tendon healing.. Clin Orthop Relat Res 1999 Oct;(367 Suppl):S312-23.
- Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA. Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model.. Am J Sports Med 2009 Nov;37(11):2126-33.
- Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I. Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing.. Cell Tissue Res 2008 Jun;332(3):469-78.
- Chong AK, Ang AD, Goh JC, Hui JH, Lim AY, Lee EH, Lim BH. Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model.. J Bone Joint Surg Am 2007 Jan;89(1):74-81.
- Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ. 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.. J Orthop Res 2009 Oct;27(10):1392-8.
- Lacitignola L, Crovace A, Rossi G, Francioso E. Cell therapy for tendinitis, experimental and clinical report.. Vet Res Commun 2008 Sep;32 Suppl 1:S33-8.
- Nixon AJ, Dahlgren LA, Haupt JL, Yeager AE, Ward DL. Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis.. Am J Vet Res 2008 Jul;69(7):928-37.
- Crovace A, Lacitignola L, Francioso E, Rossi G. Histology and immunohistochemistry study of ovine tendon grafted with cBMSCs and BMMNCs after collagenase-induced tendinitis.. Vet Comp Orthop Traumatol 2008;21(4):329-36.
- Smith RK. Mesenchymal stem cell therapy for equine tendinopathy.. Disabil Rehabil 2008;30(20-22):1752-8.
- Smith RK, Korda M, Blunn GW, Goodship AE. Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment.. Equine Vet J 2003 Jan;35(1):99-102.
- Beredjiklian PK, Favata M, Cartmell JS, Flanagan CL, Crombleholme TM, Soslowsky LJ. Regenerative versus reparative healing in tendon: a study of biomechanical and histological properties in fetal sheep.. Ann Biomed Eng 2003 Nov;31(10):1143-52.
- Chen X, Song XH, Yin Z, Zou XH, Wang LL, Hu H, Cao T, Zheng M, Ouyang HW. Stepwise differentiation of human embryonic stem cells promotes tendon regeneration by secreting fetal tendon matrix and differentiation factors.. Stem Cells 2009 Jun;27(6):1276-87.
- Talbot NC, Blomberg Le Ann. The pursuit of ES cell lines of domesticated ungulates.. Stem Cell Rev 2008 Sep;4(3):235-54.
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.. Cell 2006 Aug 25;126(4):663-76.
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors.. Cell 2007 Nov 30;131(5):861-72.
- Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells.. Science 2007 Dec 21;318(5858):1917-20.
- Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells.. Nature 2007 Jul 19;448(7151):313-7.
- Dahlgren LA, Mohammed HO, Nixon AJ. Expression of insulin-like growth factor binding proteins in healing tendon lesions.. J Orthop Res 2006 Feb;24(2):183-92.
- Dahlgren LA, Mohammed HO, Nixon AJ. Temporal expression of growth factors and matrix molecules in healing tendon lesions.. J Orthop Res 2005 Jan;23(1):84-92.
- Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue.. Biochim Biophys Acta 1986 Sep 4;883(2):173-7.
- Kim YJ, Sah RL, Doong JY, Grodzinsky AJ. Fluorometric assay of DNA in cartilage explants using Hoechst 33258.. Anal Biochem 1988 Oct;174(1):168-76.
- Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons.. J Orthop Res 2007 Feb;25(2):230-40.
- Blunden A, Murray R, Dyson S. Lesions of the deep digital flexor tendon in the digit: a correlative MRI and post mortem study in control and lame horses.. Equine Vet J 2009 Jan;41(1):25-33.
- Henegariu O, Bray-Ward P, Ward DC. Custom fluorescent-nucleotide synthesis as an alternative method for nucleic acid labeling.. Nat Biotechnol 2000 Mar;18(3):345-8.
- Movin T, Gad A, Reinholt FP, Rolf C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients.. Acta Orthop Scand 1997 Apr;68(2):170-5.
- Maffulli N, Longo UG, Franceschi F, Rabitti C, Denaro V. Movin and Bonar scores assess the same characteristics of tendon histology.. Clin Orthop Relat Res 2008 Jul;466(7):1605-11.
- Cook JL, Feller JA, Bonar SF, Khan KM. Abnormal tenocyte morphology is more prevalent than collagen disruption in asymptomatic athletes' patellar tendons.. J Orthop Res 2004 Mar;22(2):334-8.
- Smith RK, Webbon PM. Harnessing the stem cell for the treatment of tendon injuries: heralding a new dawn?. Br J Sports Med 2005 Sep;39(9):582-4.
- Trudel G, Doherty GP, Koike Y, Ramachandran N, Lecompte M, Dinh L, Uhthoff HK. Restoration of strength despite low stress and abnormal imaging after Achilles injury.. Med Sci Sports Exerc 2009 Nov;41(11):2009-16.
- Gärdin A, Bruno J, Movin T, Kristoffersen-Wiberg M, Shalabi A. Magnetic resonance signal, rather than tendon volume, correlates to pain and functional impairment in chronic Achilles tendinopathy.. Acta Radiol 2006 Sep;47(7):718-24.
- Soslowsky LJ, Carpenter JE, DeBano CM, Banerji I, Moalli MR. Development and use of an animal model for investigations on rotator cuff disease.. J Shoulder Elbow Surg 1996 Sep-Oct;5(5):383-92.
- Williams IF, McCullagh KG, Goodship AE, Silver IA. Studies on the pathogenesis of equine tendonitis following collagenase injury.. Res Vet Sci 1984 May;36(3):326-38.
- Lake SP, Ansorge HL, Soslowsky LJ. Animal models of tendinopathy.. Disabil Rehabil 2008;30(20-22):1530-41.
- Koch TG, Betts DH. Stem cell therapy for joint problems using the horse as a clinically relevant animal model.. Expert Opin Biol Ther 2007 Nov;7(11):1621-6.
- Maffulli N, Ewen SW, Waterston SW, Reaper J, Barrass V. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing.. Am J Sports Med 2000 Jul-Aug;28(4):499-505.
- Dahlgren LA, Brower-Toland BD, Nixon AJ. Cloning and expression of type III collagen in normal and injured tendons of horses.. Am J Vet Res 2005 Feb;66(2):266-70.
- Asundi KR, King KB, Rempel DM. Evaluation of gene expression through qRT-PCR in cyclically loaded tendons: an in vivo model.. Eur J Appl Physiol 2008 Feb;102(3):265-70.
- Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses.. Blood 2005 Feb 15;105(4):1815-22.
- Kopyov OV, Jacques D, Lieberman A, Duma CM, Rogers RL. Clinical study of fetal mesencephalic intracerebral transplants for the treatment of Parkinson's disease.. Cell Transplant 1996 Mar-Apr;5(2):327-37.
- Religa P, Bojakowski K, Bojakowska M, Gaciong Z, Thyberg J, Hedin U. Allogenic immune response promotes the accumulation of host-derived smooth muscle cells in transplant arteriosclerosis.. Cardiovasc Res 2005 Feb 1;65(2):535-45.
- Scott DM, Ehrmann IE, Ellis PS, Chandler PR, Simpson E. Why do some females reject males? The molecular basis for male-specific graft rejection.. J Mol Med (Berl) 1997 Feb;75(2):103-14.
- Guest DJ, Smith MR, Allen WR. Monitoring the fate of autologous and allogeneic mesenchymal progenitor cells injected into the superficial digital flexor tendon of horses: preliminary study.. Equine Vet J 2008 Mar;40(2):178-81.
Citations
This article has been cited 46 times.- Jeannerat A, Meuli J, Peneveyre C, Jaccoud S, Chemali M, Thomas A, Liao Z, Abdel-Sayed P, Scaletta C, Hirt-Burri N, Applegate LA, Raffoul W, Laurent A. Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine. Pharmaceutics 2023 Jul 3;15(7).
- Wei B, Ji M, Lin Y, Wang S, Liu Y, Geng R, Hu X, Xu L, Li Z, Zhang W, Lu J. Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo. Stem Cell Res Ther 2023 Apr 26;14(1):104.
- Yuan Z, Yu H, Long H, Dai Y, Shi L, Zhao J, Guo A, Diao N, Ma L, Yin H. Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair. Stem Cells Int 2023;2023:3656498.
- Zhang G, Zhou X, Hu S, Jin Y, Qiu Z. Large animal models for the study of tendinopathy. Front Cell Dev Biol 2022;10:1031638.
- Ramires LC, Jeyaraman M, Muthu S, Shankar A N, Santos GS, da Fonseca LF, Lana JF, Rajendran RL, Gangadaran P, Jogalekar MP, Cardoso AA, Eickhoff A. Application of Orthobiologics in Achilles Tendinopathy: A Review. Life (Basel) 2022 Mar 9;12(3).
- Laurent A, Porcello A, Fernandez PG, Jeannerat A, Peneveyre C, Abdel-Sayed P, Scaletta C, Hirt-Burri N, Michetti M, de Buys Roessingh A, Raffoul W, Allémann E, Jordan O, Applegate LA. Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders. Pharmaceutics 2021 Dec 19;13(12).
- Li ZJ, Yang QQ, Zhou YL. Basic Research on Tendon Repair: Strategies, Evaluation, and Development. Front Med (Lausanne) 2021;8:664909.
- 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.
- Laurent A, Abdel-Sayed P, Grognuz A, Scaletta C, Hirt-Burri N, Michetti M, de Buys Roessingh AS, Raffoul W, Kronen P, Nuss K, von Rechenberg B, Applegate LA, Darwiche SE. Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation. Biomedicines 2021 Apr 3;9(4).
- 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.
- Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ. Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes. Stem Cell Res Ther 2020 May 19;11(1):184.
- Chung MJ, Park S, Son JY, Lee JY, Yun HH, Lee EJ, Lee EM, Cho GJ, Lee S, Park HS, Jeong KS. Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use. Cell Cycle 2019 Nov;18(21):2954-2971.
- Magri C, Schramme M, Febre M, Cauvin E, Labadie F, Saulnier N, François I, Lechartier A, Aebischer D, Moncelet AS, Maddens S. Comparison of efficacy and safety of single versus repeated intra-articular injection of allogeneic neonatal mesenchymal stem cells for treatment of osteoarthritis of the metacarpophalangeal/metatarsophalangeal joint in horses: A clinical pilot study. PLoS One 2019;14(8):e0221317.
- 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.
- Kovac M, Litvin YA, Aliev RO, Zakirova EY, Rutland CS, Kiyasov AP, Rizvanov AA. Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment of Naturally Occurring Tendinitis and Desmitis in Horses. Front Pharmacol 2018;9:978.
- 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.
- Pöschke A, Krähling B, Failing K, Staszyk C. Molecular Characteristics of the Equine Periodontal Ligament. Front Vet Sci 2017;4:235.
- Carballo CB, Lebaschi A, Rodeo SA. Cell-based approaches for augmentation of tendon repair. Tech Shoulder Elb Surg 2017 Sep;18(3):e6-e14.
- Schröck C, Eydt C, Geburek F, Kaiser L, Päbst F, Burk J, Pfarrer C, Staszyk C. Bone marrow-derived multipotent mesenchymal stromal cells from horses after euthanasia. Vet Med Sci 2017 Nov;3(4):239-251.
- Watts AE, Millar NL, Platt J, Kitson SM, Akbar M, Rech R, Griffin J, Pool R, Hughes T, McInnes IB, Gilchrist DS. MicroRNA29a Treatment Improves Early Tendon Injury. Mol Ther 2017 Oct 4;25(10):2415-2426.
- Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM. Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial. Stem Cell Res Ther 2017 Jun 5;8(1):129.
- Bertone AL, Reisbig NA, Kilborne AH, Kaido M, Salmanzadeh N, Lovasz R, Sizemore JL, Scheuermann L, Kopp RJ, Zekas LJ, Brokken MT. Equine Dental Pulp Connective Tissue Particles Reduced Lameness in Horses in a Controlled Clinical Trial. Front Vet Sci 2017;4:31.
- Gromova A, Voronov DA, Yoshida M, Thotakura S, Meech R, Dartt DA, Makarenkova HP. Lacrimal Gland Repair Using Progenitor Cells. Stem Cells Transl Med 2017 Jan;6(1):88-98.
- 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.
- Dex S, Lin D, Shukunami C, Docheva D. Tenogenic modulating insider factor: Systematic assessment on the functions of tenomodulin gene. Gene 2016 Aug 1;587(1):1-17.
- Langhans MT, Yu S, Tuan RS. Stem Cells in Skeletal Tissue Engineering: Technologies and Models. Curr Stem Cell Res Ther 2016;11(6):453-474.
- Docheva D, Müller SA, Majewski M, Evans CH. Biologics for tendon repair. Adv Drug Deliv Rev 2015 Apr;84:222-39.
- 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.
- Tang QM, Chen JL, Shen WL, Yin Z, Liu HH, Fang Z, Heng BC, Ouyang HW, Chen X. Fetal and adult fibroblasts display intrinsic differences in tendon tissue engineering and regeneration. Sci Rep 2014 Jul 3;4:5515.
- Zhao C, Ozasa Y, Reisdorf RL, Thoreson AR, Jay GD, An KN, Amadio PC. CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine model. Clin Orthop Relat Res 2014 Sep;472(9):2569-78.
- Behfar M, Javanmardi S, Sarrafzadeh-Rezaei F. Comparative study on functional effects of allotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair: a biomechanical study in rabbits. Cell J 2014 Fall;16(3):263-70.
- Müller SA, Todorov A, Heisterbach PE, Martin I, Majewski M. Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering. Knee Surg Sports Traumatol Arthrosc 2015 Jul;23(7):2097-105.
- 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.
- Filomeno P, Dayan V, Touriño C. Stem cell research and clinical development in tendon repair. Muscles Ligaments Tendons J 2012 Jul;2(3):204-11.
- 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.
- 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.
- 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.
- Locke P, Tuan RS, O'Brien T. Stem Cell Research & Therapy in 2012. Stem Cell Res Ther 2012;3(2):16.
- Young M. Stem cell applications in tendon disorders: a clinical perspective. Stem Cells Int 2012;2012:637836.
- Hackett CH, Fortier LA. Embryonic stem cells and iPS cells: sources and characteristics. Vet Clin North Am Equine Pract 2011 Aug;27(2):233-42.
- Cassano JM, Leonard BC, Martins BC, Vapniarsky N, Morgan JT, Dow SW, Wotman KL, Pezzanite LM. Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis. Front Vet Sci 2023;10:1293199.
- Ren X, Zhuang H, Zhang Y, Zhou P. Cerium oxide nanoparticles-carrying human umbilical cord mesenchymal stem cells counteract oxidative damage and facilitate tendon regeneration. J Nanobiotechnology 2023 Oct 3;21(1):359.
- Li H, Xiong S, Masieri FF, Monika S, Lethaus B, Savkovic V. Mesenchymal Stem Cells Isolated from Equine Hair Follicles Using a Method of Air-Liquid Interface. Stem Cell Rev Rep 2023 Nov;19(8):2943-2956.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists