Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair.
Abstract: The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in peritenon cells. Cells from the peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the peritenon have substantial potential to influence tendon-healing outcome, warranting further scrutiny of their role.
Publication Date: 2014-03-20 PubMed ID: 24651449PubMed Central: PMC3961373DOI: 10.1371/journal.pone.0092474Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study closely examines and compares the healing potentials of cell populations derived from the peritenon (the outer layer of a tendon) and the tendon core. The investigations suggest that cells from the peritenon display larger ability regarding adipogenic and osteogenic differentiation, faster migration, quicker replication, and a higher potential to differentiate into a myofibroblastic phenotype, possibly implying a substantial role in tendon healing.
Objective of the Study
- The research attempts to contribute to the understanding of the healing process in injured tendons, specifically focusing on the differing roles and potentials of cells extracted from the peritenon and those from the tendon core.
Methodology
- Cell characterization was done for two types of cells: those derived from the peritenon (contributing to extrinsic healing) and those derived from the tendon core (contributing to intrinsic healing). The cells were sourced from a horse’s superficial digital flexor tendon.
- Cell plasticity, proliferative capacity, and migration characteristics stood as measures to determine their healing potential. Additionally, markers for tenogenic and matrix remodeling were studied.
- Experiments including colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses were performed to investigate markers of osteogenic and adipogenic differentiation after culture in induction media.
- The capacities of the cells to differentiate into a myofibroblastic phenotype were also evaluated.
Results and Conclusion
- Results identified a capacity in both peritenon- and tendon-derived cell populations for adipogenic and osteogenic differentiation.
- The peritenon-derived cells demonstrated a higher expression of progenitor cell markers, in comparison to cells from the tendon core.
- Additionally, the peritenon cells migrated faster, replicated more quickly, and showed a higher potential to differentiate into a myofibroblastic phenotype.
- Concluding their study, the researchers suggested that the peritenon-derived cells carry a significant potential to impact the outcome of tendon healing. Thus, the role and therapeutic application of these cells warrant further study and scrutiny.
Cite This Article
APA
Cadby JA, Buehler E, Godbout C, van Weeren PR, Snedeker JG.
(2014).
Differences between the cell populations from the peritenon and the tendon core with regard to their potential implication in tendon repair.
PLoS One, 9(3), e92474.
https://doi.org/10.1371/journal.pone.0092474 Publication
Researcher Affiliations
- Department of Orthopaedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Department Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland; Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Department of Orthopaedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Department Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.
- Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, Q, Canada.
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Department of Orthopaedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Department Health Sciences and Technology, Swiss Federal Institute of Technology, Zurich, Switzerland.
MeSH Terms
- Adipogenesis
- Animals
- Biomarkers
- Cell Culture Techniques
- Cell Differentiation
- Cell Movement
- Cell Proliferation
- Colony-Forming Units Assay
- Gene Expression Profiling
- Gene Expression Regulation
- Horses
- Myofibroblasts / cytology
- Myofibroblasts / metabolism
- Osteogenesis
- Stem Cells / cytology
- Tendon Injuries / genetics
- Tendon Injuries / metabolism
- Tendon Injuries / therapy
- Tendons / cytology
- Tendons / metabolism
- Wound Healing / physiology
Conflict of Interest Statement
The authors have declared that no competing interests exist.
References
This article includes 47 references
- Jung HJ, Fisher MB, Woo SL. Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons.. Sports Med Arthrosc Rehabil Ther Technol 2009 May 20;1(1):9.
- Pierre-Jerome C, Moncayo V, Terk MR. MRI of the Achilles tendon: a comprehensive review of the anatomy, biomechanics, and imaging of overuse tendinopathies.. Acta Radiol 2010 May;51(4):438-54.
- Rees JD, Maffulli N, Cook J. Management of tendinopathy.. Am J Sports Med 2009 Sep;37(9):1855-67.
- SKOOG T, PERSSON BH. An experimental study of the early healing of tendons.. Plast Reconstr Surg (1946) 1954 May;13(5):384-99.
- POTENZA AD. PREVENTION OF ADHESIONS TO HEALING DIGITAL FLEXOR TENDONS.. JAMA 1964 Jan 18;187:187-91.
- Kannus P. Structure of the tendon connective tissue.. Scand J Med Sci Sports 2000 Dec;10(6):312-20.
- Eiken O, Lundborg G, Rank F. The role of the digital synovial sheath in tendon grafting. An experimental and clinical study on autologous tendon grafting in the digit.. Scand J Plast Reconstr Surg 1975;9(3):182-9.
- Matthews P, Richards H. The repair potential of digital flexor tendons. An experimental study.. J Bone Joint Surg Br 1974 Nov;56-B(4):618-25.
- Furlow LT Jr. The role of tendon tissues in tendon healing.. Plast Reconstr Surg 1976 Jan;57(1):39-49.
- Lundborg G, Rank F. Experimental intrinsic healing of flexor tendons based upon synovial fluid nutrition.. J Hand Surg Am 1978 Jan;3(1):21-31.
- Mienaltowski MJ, Adams SM, Birk DE. Regional differences in stem cell/progenitor cell populations from the mouse achilles tendon.. Tissue Eng Part A 2013 Jan;19(1-2):199-210.
- Kajikawa Y, Morihara T, Watanabe N, Sakamoto H, Matsuda K, Kobayashi M, Oshima Y, Yoshida A, Kawata M, Kubo T. GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing.. J Cell Physiol 2007 Mar;210(3):684-91.
- Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair.. J Bone Joint Surg Am 2005 Jan;87(1):187-202.
- Caplan AI, Bruder SP. Mesenchymal stem cells: building blocks for molecular medicine in the 21st century.. Trends Mol Med 2001 Jun;7(6):259-64.
- de Mos M, Koevoet WJ, Jahr H, Verstegen MM, Heijboer MP, Kops N, van Leeuwen JP, Weinans H, Verhaar JA, van Osch GJ. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study.. BMC Musculoskelet Disord 2007 Feb 23;8:16.
- Khan KM, Cook JL, Bonar F, Harcourt P, Astrom M. Histopathology of common tendinopathies. Update and implications for clinical management.. Sports Med 1999 Jun;27(6):393-408.
- Gohr CM, Fahey M, Rosenthal AK. Calcific tendonitis : a model.. Connect Tissue Res 2007;48(6):286-91.
- Hinz B, Gabbiani G, Chaponnier C. The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo.. J Cell Biol 2002 May 13;157(4):657-63.
- Kvist M, Józsa L, Järvinen M, Kvist H. Fine structural alterations in chronic Achilles paratenonitis in athletes.. Pathol Res Pract 1985 Oct;180(4):416-23.
- Järvinen M, Józsa L, Kannus P, Järvinen TL, Kvist M, Leadbetter W. Histopathological findings in chronic tendon disorders.. Scand J Med Sci Sports 1997 Apr;7(2):86-95.
- Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro.. Nat Protoc 2006;1(5):2315-9.
- Mos Md. Tendon cell behavior and matrix remodeling in degerative tendinopathy. .
- Lovati AB, Corradetti B, Lange Consiglio A, Recordati C, Bonacina E, Bizzaro D, Cremonesi F. Characterization and differentiation of equine tendon-derived progenitor cells.. J Biol Regul Homeost Agents 2011 Apr-Jun;25(2 Suppl):S75-84.
- Guest DJ, Ousey JC, Smith MR. Defining the expression of marker genes in equine mesenchymal stromal cells.. Stem Cells Cloning 2008;1:1-9.
- Penny J, Harris P, Shakesheff KM, Mobasheri A. The biology of equine mesenchymal stem cells: phenotypic characterization, cell surface markers and multilineage differentiation.. Front Biosci (Landmark Ed) 2012 Jan 1;17(3):892-908.
- Zhang YW, Davis EG, Bai J. Determination of internal control for gene expression studies in equine tissues and cell culture using quantitative RT-PCR.. Vet Immunol Immunopathol 2009 Jul 15;130(1-2):114-9.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
- Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.. J Cell Biol 1986 Dec;103(6 Pt 2):2787-96.
- Amiel D, Gelberman R, Harwood F, Siegel D. Fibronectin in healing flexor tendons subjected to immobilization or early controlled passive motion.. Matrix 1991 Jun;11(3):184-9.
- Gelberman RH, Amiel D, Harwood F. Genetic expression for type I procollagen in the early stages of flexor tendon healing.. J Hand Surg Am 1992 May;17(3):551-8.
- Harrison RK, Mudera V, Grobbelaar AO, Jones ME, McGrouther DA. Synovial sheath cell migratory response to flexor tendon injury: an experimental study in rats.. J Hand Surg Am 2003 Nov;28(6):987-93.
- 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.
- Taylor SH, Al-Youha S, Van Agtmael T, Lu Y, Wong J, McGrouther DA, Kadler KE. Tendon is covered by a basement membrane epithelium that is required for cell retention and the prevention of adhesion formation.. PLoS One 2011 Jan 26;6(1):e16337.
- Jones DL, Wagers AJ. No place like home: anatomy and function of the stem cell niche.. Nat Rev Mol Cell Biol 2008 Jan;9(1):11-21.
- Harris MT, Butler DL, Boivin GP, Florer JB, Schantz EJ, Wenstrup RJ. Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructs.. J Orthop Res 2004 Sep;22(5):998-1003.
- Violini S, Ramelli P, Pisani LF, Gorni C, Mariani P. Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12.. BMC Cell Biol 2009 Apr 22;10:29.
- Hoynowski SM, Fry MM, Gardner BM, Leming MT, Tucker JR, Black L, Sand T, Mitchell KE. Characterization and differentiation of equine umbilical cord-derived matrix cells.. Biochem Biophys Res Commun 2007 Oct 19;362(2):347-53.
- Reed SA, Johnson SE. Equine umbilical cord blood contains a population of stem cells that express Oct4 and differentiate into mesodermal and endodermal cell types.. J Cell Physiol 2008 May;215(2):329-36.
- Zhang J, Wang JH. Characterization of differential properties of rabbit tendon stem cells and tenocytes.. BMC Musculoskelet Disord 2010 Jan 18;11:10.
- Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF. Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.. Nat Med 2007 Oct;13(10):1219-27.
- Patterson-Kane JC, Becker DL, Rich T. The pathogenesis of tendon microdamage in athletes: the horse as a natural model for basic cellular research.. J Comp Pathol 2012 Aug-Oct;147(2-3):227-47.
- Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification.. Cell 2006 Aug 25;126(4):677-89.
- Sharma RI, Snedeker JG. Biochemical and biomechanical gradients for directed bone marrow stromal cell differentiation toward tendon and bone.. Biomaterials 2010 Oct;31(30):7695-704.
- Ohberg L, Alfredson H. Ultrasound guided sclerosis of neovessels in painful chronic Achilles tendinosis: pilot study of a new treatment.. Br J Sports Med 2002 Jun;36(3):173-5; discussion 176-7.
- Ohberg L, Alfredson H. Sclerosing therapy in chronic Achilles tendon insertional pain-results of a pilot study.. Knee Surg Sports Traumatol Arthrosc 2003 Sep;11(5):339-43.
- Cui Q, Wang Z, Jiang D, Qu L, Guo J, Li Z. HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat.. Eur J Appl Physiol 2011 Jul;111(7):1457-63.
- Salingcarnboriboon R, Yoshitake H, Tsuji K, Obinata M, Amagasa T, Nifuji A, Noda M. Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property.. Exp Cell Res 2003 Jul 15;287(2):289-300.
Citations
This article has been cited 25 times.- Peniche Silva CJ, De La Vega RE, Panos J, Joris V, Evans CH, Balmayor ER, van Griensven M. MiRNAs as Potential Regulators of Enthesis Healing: Findings in a Rodent Injury Model.. Int J Mol Sci 2023 May 10;24(10).
- Dos Anjos EHM, Mello MLS, Vidal BC. High-Performance Polarization Microscopy Reveals Structural Remodeling in Rat Calcaneal Tendons Cultivated In Vitro.. Cells 2023 Feb 10;12(4).
- Hart DA, Ahmed AS, Ackermann P. Optimizing repair of tendon ruptures and chronic tendinopathies: Integrating the use of biomarkers with biological interventions to improve patient outcomes and clinical trial design.. Front Sports Act Living 2022;4:1081129.
- Fung A, Sun M, Soslowsky LJ, Birk DE. Targeted conditional collagen XII deletion alters tendon function.. Matrix Biol Plus 2022 Dec;16:100123.
- Baldwin MJ, Mimpen JY, Cribbs AP, Stace E, Philpott M, Dakin SG, Carr AJ, Snelling SJ. Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts.. Front Bioeng Biotechnol 2021;9:795748.
- Zhou X, Li J, Giannopoulos A, Kingham PJ, Backman LJ. Secretome from In Vitro Mechanically Loaded Myoblasts Induces Tenocyte Migration, Transition to a Fibroblastic Phenotype and Suppression of Collagen Production.. Int J Mol Sci 2021 Dec 3;22(23).
- Bobzin L, Roberts RR, Chen HJ, Crump JG, Merrill AE. Development and maintenance of tendons and ligaments.. Development 2021 Apr 15;148(8).
- Quam VG, Altmann NN, Brokken MT, Durgam SS. Zonal characterization and differential trilineage potentials of equine intrasynovial deep digital flexor tendon-derived cells.. BMC Vet Res 2021 Apr 1;17(1):138.
- Depuydt E, Broeckx SY, Van Hecke L, Chiers K, Van Brantegem L, van Schie H, Beerts C, Spaas JH, Pille F, Martens A. The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model.. Front Vet Sci 2021;8:641441.
- Huang Z, Yin Z, Xu J, Fei Y, Heng BC, Jiang X, Chen W, Shen W. Tendon Stem/Progenitor Cell Subpopulations and Their Implications in Tendon Biology.. Front Cell Dev Biol 2021;9:631272.
- Zhang J, Li F, Williamson KM, Tan S, Scott D, Onishi K, Hogan MV, Wang JH. Characterization of the structure, vascularity, and stem/progenitor cell populations in porcine Achilles tendon (PAT).. Cell Tissue Res 2021 May;384(2):367-387.
- Pechanec MY, Boyd TN, Baar K, Mienaltowski MJ. Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro.. BMC Musculoskelet Disord 2020 Sep 23;21(1):627.
- Rajpar I, Barrett JG. Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells.. Stem Cell Res Ther 2020 Apr 9;11(1):152.
- Kisiday JD, Liebig BE, Goodrich LR. Adult ovine chondrocytes in expansion culture adopt progenitor cell properties that are favorable for cartilage tissue engineering.. J Orthop Res 2020 Sep;38(9):1996-2005.
- Tan GK, Pryce BA, Stabio A, Brigande JV, Wang C, Xia Z, Tufa SF, Keene DR, Schweitzer R. Tgfβ signaling is critical for maintenance of the tendon cell fate.. Elife 2020 Jan 21;9.
- Nichols AEC, Best KT, Loiselle AE. The cellular basis of fibrotic tendon healing: challenges and opportunities.. Transl Res 2019 Jul;209:156-168.
- Qu F, Guilak F, Mauck RL. Cell migration: implications for repair and regeneration in joint disease.. Nat Rev Rheumatol 2019 Mar;15(3):167-179.
- Imai S, Kumagai K, Yamaguchi Y, Miyatake K, Saito T. Platelet-Rich Plasma Promotes Migration, Proliferation, and the Gene Expression of Scleraxis and Vascular Endothelial Growth Factor in Paratenon-Derived Cells In Vitro.. Sports Health 2019 Mar Apr;11(2):142-148.
- Bergante S, Creo P, Piccoli M, Ghiroldi A, Menon A, Cirillo F, Rota P, Monasky MM, Ciconte G, Pappone C, Randelli P, Anastasia L. GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells.. Stem Cells Int 2018;2018:4706943.
- Ackerman JE, Best KT, O'Keefe RJ, Loiselle AE. Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing.. Sci Rep 2017 Aug 17;7(1):8658.
- Linderman SW, Gelberman RH, Thomopoulos S, Shen H. Cell and Biologic-Based Treatment of Flexor Tendon Injuries.. Oper Tech Orthop 2016 Sep;26(3):206-215.
- Runesson E, Ackermann P, Karlsson J, Eriksson BI. Nucleostemin- and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing.. BMC Musculoskelet Disord 2015 Aug 20;16:212.
- Lui PP. Markers for the identification of tendon-derived stem cells in vitro and tendon stem cells in situ - update and future development.. Stem Cell Res Ther 2015 Jun 2;6(1):106.
- Williamson KA, Lee KJ, Humphreys WJ, Comerford EJ, Clegg PD, Canty-Laird EG. Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT).. J Orthop Res 2015 Jun;33(6):849-58.
- Screen HR, Berk DE, Kadler KE, Ramirez F, Young MF. Tendon functional extracellular matrix.. J Orthop Res 2015 Jun;33(6):793-9.
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