Soft-Focused Extracorporeal Shock Waves Increase the Expression of Tendon-Specific Markers and the Release of Anti-inflammatory Cytokines in an Adherent Culture Model of Primary Human Tendon Cells

Girolamo, Laura de; Stanco, D.; Galliera, Emanuela; Viganò, Marco; Lovati, Arianna B.; Marazzi, Monica Gioia; Romeo, Placido; Sansone, Valerio

doi:10.1016/j.ultrasmedbio.2013.12.003

Cited by 40 publications

(27 citation statements)

References 51 publications

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“…The choice of the collagenase doses included in this work was based on our previous in vitro studies, in which the dose inducing the collagen fiber disruption was validated in tendon explants [31, 32]. …”

Section: Discussionmentioning

confidence: 99%

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

et al. 2016

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Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions. Despite the relevant social impact, both pathogenesis and development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. The purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies. With this purpose, 40 Sprague Dawley rats were randomly divided into two groups, treated by injecting collagenase type I within the Achilles tendon at 1 mg/mL (low dose) or 3 mg/mL (high dose). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days. Our results revealed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater neovascularization and fatty degeneration with respect to the lower dose. These changes were found to be time-dependent and to resemble the features of human tendinopathy. Indeed, in our series, the acute phase occurred from day 3 to day 15, and then progressed towards the proliferative phase from day 30 to day 45 displaying a degenerative appearance associated with a very precocious and mild remodeling process. The model represents a good balance between similarity with histological features of human tendinopathy and feasibility, in terms of tendon size to create lesions and costs when compared to other animal models. Moreover, this model could contribute to improve the knowledge in this field, and it could be useful to properly design further pre-clinical studies to test innovative treatments for tendinopathy.

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Section: Discussionmentioning

confidence: 99%

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

et al. 2016

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“…Moreover, ESW application significantly accelerated hTSPCs differentiation, thus suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury [68]. Indeed, these observations were confirmed in a different in vitro setting, where, TSPCs treated with ESW showed increased proliferation, expression of tendon specific markers (scleraxis and collagen type I) and production of growth factors (VEGF, TGFβ) and cytokines (IL-10), consistently with the instauration of a regenerative and anti-inflammatory microenvironment [69]. Very recently, Rinella and co-authors were able to demonstrate how ESWT would inhibit the development of a myofibroblast phenotype in human ASCs.…”

Section: Extracorporeal Shock Wave Therapymentioning

confidence: 95%

Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders

et al. 2016

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BackgroundMusculoskeletal disorders are regarded as a major cause of worldwide morbidity and disability, and they result in huge costs for national health care systems. Traditional therapies frequently turned out to be poorly effective in treating bone, cartilage, and tendon disorders or joint degeneration. As a consequence, the development of novel biological therapies that can treat more effectively these conditions should be the highest priority in regenerative medicine.Main body of the abstractMesenchymal stem cells (MSCs) represent one of the most promising tools in musculoskeletal tissue regenerative medicine, thanks to their proliferation and differentiation potential and their immunomodulatory and trophic ability. Indeed, MSC-based approaches have been proposed for the treatment of almost all orthopedic conditions, starting from different cell sources, alone or in combination with scaffolds and growth factors, and in one-step or two-step procedures. While all these approaches would require cell harvesting and transplantation, the possibility to stimulate the endogenous MSCs to enhance their tissue homeostasis activity represents a less-invasive and cost-effective therapeutic strategy. Nowadays, the role of tissue-specific resident stem cells as possible therapeutic target in degenerative pathologies is underinvestigated. Biophysical stimulations, and in particular extracorporeal shock waves treatment and pulsed electromagnetic fields, are able to induce proliferation and support differentiation of MSCs from different origins and affect their paracrine production of growth factors and cytokines.Short conclusionsThe present review reports the attempts to exploit the resident stem cell potential in musculoskeletal pathologies, highlighting the role of MSCs as therapeutic target of currently applied biophysical treatments.

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“…Specifically, the energy flux density of pressure waves delivered using a radial handpiece is highest at the applicator tip and reduces the further it travels due to a convex waveform (current study), whereas pressure waves delivered using a focused handpiece converge to concentrate energy at a specific depth (Schmitz et al, 2013). Currently, there is a lack of research detailing the significance of pressure wave shape and delivery method on tendon tissue biology (Maier and Schmitz, 2008;van der Worp et al, 2013), although the response of tenocyte monolayers to soft-focused shockwaves (a third type of shockwave which maintains the temporal characteristics of a focused shockwave, but applies the stimulus to a larger focal area) was recently examined (de Girolamo et al, 2014). Not only did this study deliver the same total energy as the current study, but the monolayer provided some cell-to-cell contact which is important for mechanotransduction.…”

Section: Inflammatory Cytokinesmentioning

confidence: 99%

In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

Waugh

Morrissey

Jones³

et al. 2015

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Extracorporeal shock wave therapy (ESWT) is a noninvasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session of ESWT was administered to the mid-portion of the Achilles tendon in thirteen healthy individuals (aged 25.7 ± 7.0 years) and patellar or Achilles tendon of six patients with tendinopathies (aged 39.0 ± 14.9 years). Dialysate samples from the surrounding peri-tendon were collected before and immediately after ESWT. Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, vascular endothelial growth factor and interferon-γ were quantified using a cytometric bead array while gelatinase activity (MMP-2 and -9) was examined using zymography. There were no statistical differences between the biological tissue response to ESWT in healthy and pathological tendons. IL-1β, IL-2, IL-6 and IL-8 were the cytokines predominantly detected in the tendon dialysate. IL-1β and IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were elevated immediately after ESWT and remained significantly elevated for four hours post-ESWT (p < 0.001). Proforms of MMP-2 and -9 also increased after ESWT (p < 0.003), whereas there were no significant changes in active MMP forms. In addition, the biological response to ESWT treatment could be differentiated between possible responders and non-responders based on a minimum 5-fold increase in any inflammatory marker or MMP from pre-to post-ESWT. Our findings provide novel evidence of the biological mechanisms underpinning ESWT in humans in vivo. They suggest that the mechanical stimulus provided by ESWT might aid tendon remodelling in tendinopathy by promoting the inflammatory and catabolic processes that are associated with removing damaged matrix constituents. The non-response of some individuals may help to explain why ESWT does not improve symptoms in all patients and provides a potential focus for future research.

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Soft-Focused Extracorporeal Shock Waves Increase the Expression of Tendon-Specific Markers and the Release of Anti-inflammatory Cytokines in an Adherent Culture Model of Primary Human Tendon Cells

Cited by 40 publications

References 51 publications

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

Dose-Related and Time-Dependent Development of Collagenase-Induced Tendinopathy in Rats

Mesenchymal stem cells as therapeutic target of biophysical stimulation for the treatment of musculoskeletal disorders

In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

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