Exploring Stem Cells and Inflammation in Tendon Repair and Regeneration
Tendon injuries are frequent and are responsible for substantial morbidity both in sports and in the workplace. Despite the endogenous mechanisms of tendon repair and regeneration, tendon healing upon injury is slow and often insufficient to restore complete biomechanics functionality.
Inflammation has a pivotal role in tendon healing and failed healing responses contribute to the progression of tendinopathies. However, the molecular and cellular mechanisms involved are poorly understood requiring further insights.
During inflammation, bioactive molecules such as cytokines secreted locally at the injury site, influence resident stem cells that contribute as modulatory agents over the niche towards homeostasis, holding great promise as therapeutic agents for tendon pathological conditions associated to unresolved inflammation and failed healing.
This review overviews the role of cytokines and resident cells, focusing on the participation of tendon stem cell population in inflammation and tendon healing upon injury and their potential action in resolution of pathological conditions.
KeywordsCytokines Healing Inflammation Mechanical stimulation Pathology Repair Tendon Tenocytes
connective tissue growth factor
mesenchymal stem/stromal cell
activator of transcription 3
tendon-derived stem cells
The authors acknowledge the financial support from Fundação para a Ciência e Tecnologia (FCT) for the doctoral grant PD/BD/128089/2016, the project NORTE-01-0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020) and HORIZON 2020 under the TEAMING GRANT agreement No 739572 – The Discoveries CTR.
- Dean BJF, Dakin SG, Millar NL, Carr AJ (2017) Review- emerging concepts in the pathogenesis of tendinopathy. Surgeon J R Coll Surg Edinb Irel 15(6):349–354Google Scholar
- Dohnert MB, Ferreira GK, Silveira PC, Zanoni ET, Dohnert LH, de Souza CT, Paula MM (2015) Inflammatory cytokines content in Achilles tendinopathy after phonophoresis treatment combined with gold nanoparticles and diclophenac diethylammonium in rats. Inflammation 38:1044–1049CrossRefPubMedGoogle Scholar
- Harrison R, Jones M, Grobbelar AO, McGrouther DA, Brown RA, Mudera V (2003) Tendon healing intrinsic or extrinsic? Direct evidence for dual mechanisms in early stages of tendon injury. Tissue Eng 9(4):852–852Google Scholar
- Millar NL, Akbar M, Campbell AL, Reilly JH, Kerr SC, McLean M, Frleta-Gilchrist M, Fazzi UG, Leach WJ, Rooney BP, Crowe LAN, Murrell GAC, McInnes IB (2015) IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy. Sci Rep 6:1–11Google Scholar
- Riggin CN, Morris TR, Soslowsky LJ (2015) Tendinopathy II: etiology, pathology, and healing of tendon injury and disease. In: Reis M, Rodrigues MRT (eds) Tendon regeneration understanding tissue physiology and development to engineer functional substitutes. Elsevier, San DiegoGoogle Scholar
- Shen H, Kormpakis I, Havlioglu N, Linderman SW, Sakiyama-Elbert SE, Erickson IE, Zarembinski T, Silva MJ, Gelberman RH, Thomopoulos S (2016) The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing. Stem Cell Res Ther 7:144CrossRefPubMedPubMedCentralGoogle Scholar
- Speed C (2016) Metabolic influences on risk for tendon disorders. In: Ackermann PW, Hart D (eds) Metabolic influences on risk for tendon disorders, Advances in Experimental Medicine and Biology. Springer, ChamGoogle Scholar
- Zabrzyński J, Zabrzyńska A, Grzanka D (2016) Tendinopathy – a disease of tendons. J Orthop Trauma Surg Relat Res 3:024–030Google Scholar