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.

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

ConspectusElectrospinning is a simple and versatile technique that relies on the electrostatic repulsion between surface charges to continuously draw nanofibers from a viscoelastic fluid. It has been applied to successfully produce nanofibers, with diameters down to tens of nanometers, from a rich variety of materials, including polymers, ceramics, small molecules, and their combinations. In addition to solid nanofibers with a smooth surface, electrospinning has also been adapted to generate nanofibers with a number of secondary structures, including those characterized by a porous, hollow, or core–sheath structure. The surface and/or interior of such nanofibers can be further functionalized with molecular species or nanoparticles during or after an electrospinning process. In addition, electrospun nanofibers can be assembled into ordered arrays or hierarchical structures by manipulation of their alignment, stacking, and/or folding. All of these attributes make electrospun nanofibers well-suited for a bro...

/pdf/electrospun-nanofibers-new-concepts-materials-and-n7hmm5pbw3.pdf

Electrospun Nanofibers: New Concepts, Materials, and Applications

Tendon disorders are frequent, and are responsible for much morbidity both in sport and the workplace. Although the presence of degenerative changes does not always lead to symptoms, pre-existing degeneration has been implicated as a risk factor for acute tendon rupture. The term tendinopathy is a generic descriptor of the clinical conditions in and around tendons arising from overuse. The terms "tendinosis" and "tendinitis/tendonitis" should only be used after histopathological examination. Disordered healing is seen in tendinopathy, and inflammation is not typically seen. In acute injuries, the process of tendon healing is an indivisible process that can be categorized into three overlapping phases for descriptive purposes. Tendon healing can occur intrinsically, via proliferation of epitenon and endotenon tenocytes, or extrinsically, by invasion of cells from the surrounding sheath and synovium. Despite remodeling, the biochemical and mechanical properties of healed tendon tissue never match those of intact tendon. Tendon injuries account for considerable morbidity, and often prove disabling for several months, despite what is considered appropriate management. Chronic problems caused by overuse of tendons probably account for 30% of all running-related injuries, and the prevalence of elbow tendinopathy in tennis players can be as high as 40%. The basic cell biology of tendons is still not fully understood, and the management of tendon injury poses a considerable challenge for clinicians. This article describes the structure of tendons, and reviews the pathophysiology of tendon injury and healing.

Biology of tendon injury: healing, modeling and remodeling

Surgical treatment of tendon ruptures and lacerations is currently the most common therapeutic modality. Tendon repair in the hand involves a slow repair process, which results in inferior repair tissue and often a failure to obtain full active range of motion. The initial stages of repair include the formation of functionally weak tissue that is not capable of supporting tensile forces that allow early active range of motion. Immobilization of the digit or limb will promote faster healing but inevitably results in the formation of adhesions between the tendon and tendon sheath, which leads to friction and reduced gliding. Loading during the healing phase is critical to avoid these adhesions but involves increased risk of rupture of the repaired tendon. Understanding the biology and organization of the native tendon and the process of morphogenesis of tendon tissue is necessary to improve current treatment modalities. Screening the genes expressed during tendon morphogenesis and determining the growth factors most crucial for tendon development will likely lead to treatment options that result in superior repair tissue and ultimately improved functional outcomes.

Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options.

Biologics for tendon repair.

Tendon disorders are commonly seen in clinical practice Their successful treatment is difficult and patients often experience symptoms for prolonged periods of time At present the aetiology of tendon disorders remains unclear, with several factors having been implicated An improved understanding of tendon injury and healing is essential to enable focused treatment strategies to be devised

P. Sharma

Papers

Biology of tendon injury: healing, modeling and remodeling

Basic biology of tendon injury and healing