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      Current concepts on tenogenic differentiation and clinical applications

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          Summary

          Tendon is a tissue that transmits force from muscle to bone. Chronic or acute tendon injuries are very common, and are always accompanied by pain and a limited range of motion in patients. In clinical settings, management of tendon injuries still remains a big challenge. Cell therapies, such as the application of stem cells for tenogenic differentiation, were suggested to be an ideal strategy for clinical translation. However, there is still a lack of specific methods for tenogenic differentiation due to the limited understanding of tendon biology currently. This review focuses on the summary of current published strategies for tenogenic differentiation, such as the application of growth factors, mechanical stimulation, biomaterials, coculture, or induced pluripotent stem cells. Current clinical applications of stem cells for treatment of tendon injuries and their limitations have also been discussed in this review.

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          Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche.

          Yanming Bi, Driss Ehirchiou, Tina Kilts … (2007)
          The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.
          Article 0 comments Cited 437 times – based on 0 reviews     Review now
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            Tendon injury and tendinopathy: healing and repair.

            Pankaj Sharma, Nicola Maffulli (2005)
            Tendon disorders are frequent and are responsible for substantial morbidity both in sports and in the workplace. Tendinopathy, as opposed to tendinitis or tendinosis, is the best generic descriptive term for the clinical conditions in and around tendons arising from overuse. Tendinopathy is a difficult problem requiring lengthy management, and patients often respond poorly to treatment. Preexisting degeneration has been implicated as a risk factor for acute tendon rupture. Several physical modalities have been developed to treat tendinopathy. There is limited and mixed high-level evidence to support the, albeit common, clinical use of these modalities. Further research and scientific evaluation are required before biological solutions become realistic options.
            Article 0 comments Cited 216 times – based on 0 reviews     Review now
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              Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.

              R Schweitzer, J Chyung, L. Murtaugh … (2001)
              Little is known about the genesis and patterning of tendons and other connective tissues, mostly owing to the absence of early markers. We have found that Scleraxis, a bHLH transcription factor, is a highly specific marker for all the connective tissues that mediate attachment of muscle to bone in chick and mouse, including the limb tendons, and show that early scleraxis expression marks the progenitor cell populations for these tissues. In the early limb bud, the tendon progenitor population is found in the superficial proximomedial mesenchyme. Using the scleraxis gene as a marker we show that these progenitors are induced by ectodermal signals and restricted by bone morphogenetic protein (BMP) signaling within the mesenchyme. Application of Noggin protein antagonizes this endogenous BMP activity and induces ectopic scleraxis expression. However, the presence of excess tendon progenitors does not lead to the production of additional or longer tendons, indicating that additional signals are required for the final formation of a tendon. Finally, we show that the endogenous expression of noggin within the condensing digit cartilage contributes to the induction of distal tendons.
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                Author and article information

                Contributors
                Gang Li
                Journal
                Journal ID (nlm-ta): J Orthop Translat
                Journal ID (iso-abbrev): J Orthop Translat
                Title: Journal of Orthopaedic Translation
                Publisher: Chinese Speaking Orthopaedic Society
                ISSN (Print): 2214-031X
                ISSN (Electronic): 2214-0328
                Publication date PMC-release: 18 March 2017
                Publication date Collection: April 2017
                Publication date (Electronic): 18 March 2017
                Volume: 9
                Pages: 28-42
                Affiliations
                [a ]Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                [b ]Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                [c ]Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
                [d ]The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China
                Author notes
                [∗ ]Corresponding author. Department of Orthopaedics and Traumatology and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong, China.Department of Orthopaedics and Traumatology and Li Ka Shing Institute of Health SciencesPrince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinNew TerritoriesHong Kong, China gangli@ 123456cuhk.edu.hk
                Article
                Publisher ID: S2214-031X(16)30299-6
                DOI: 10.1016/j.jot.2017.02.005
                PMC ID: 5822963
                PubMed ID: 29662797
                SO-VID: 4ae2d5f5-4fb0-4646-9b1b-acf1e50f1734
                Copyright © © 2017 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 15 December 2016
                Date revision received : 21 February 2017
                Date accepted : 23 February 2017
                Categories
                Subject: Review Article

                Keywords: mesenchymal stem cells,tendon derived stem cells,tendon healing,tenogenic differentiation
                Data availability:
                Keywords: mesenchymal stem cells, tendon derived stem cells, tendon healing, tenogenic differentiation

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