Impact of age and donor sites on bioactivities of tendon cells in autologous tenocyte implantation (OrthoATI™) for treatment of chronic tendinopathy.

OBJECTIVES: Autologous tenocyte implantation (OrthoATI™) therapy has demonstrated efficacy in treating patients with tendinopathy at various anatomical sites. This study evaluates the effect of patient age, gender, and tendon biopsy site on morphology, growth, and gene expression of autologous tendon cells used to treat chronic tendinopathy. METHODS: Patients undergoing OrthoATI™ for tendinopathies between 2020 and 2022 were initially treated by biopsies taken from patella tendon (PT) or palmaris longus tendon (PL). The biopsies were sent to a Good Manufacturing Practice (GMP) cell laboratory where tendon cells were isolated, cultured, and expanded for four to six weeks. Cell morphology was assessed using phase contrast microscopy. Droplet digital PCR (ddPCR) was utilized for gene expression analysis. Dichotomous results were compared between groups using x2 or Fisher's exact tests with no adjustment for multiple comparisons. The nonparametric Mann-Whitney U and Kruskal-Wallis tests were utilized for the sex and age (<35y, 35-44y, 45-54y, >55y) analyses, respectively. All analyses were performed using IBM SPSS v27, and a two-tailed P-value of <0.05 was considered statistically significant. RESULTS: 149 patients were included in the analysis. The PT was biopsied in 63 patients, and PL in 86 patients. There were no observer effects for age and gender between the PT and PL groups. There was no statistical significance between the PT and PL tendons for cell morphology, average cell population doubling time (PDT) (PT 83.9 vs PL 82.7 â€‹h, p â€‹= â€‹0.482), cellular yield (PT 16.2 vs PL 15.2 â€‹× â€‹106, p â€‹= â€‹0.099), and cell viability (PT 98.7 vs PL 99.0%, p â€‹= â€‹0.277). Additionally, ddPCR analyses showed no statistical significance found in tenogenic gene expression, including collagen type I (COL1, p â€‹= â€‹0.86), tenomodulin (TNMD, p â€‹= â€‹0.837) and scleraxis (SCX, p â€‹= â€‹0.331) between PT- and PL-derived tendon cells. An age stratification analysis found no effect on growth and gene expression. COL1 was found to be higher in males when compared to females (P â€‹< â€‹0.001), but otherwise no difference was seen in growth and gene expression in the gender analysis. No postbiopsy clinical complications were reported for either group. CONCLUSION: This study has shown that the growth and bioactivities of tendon cells from tendon biopsies for OrthoATI™ are not affected by tendon donor site and age. LEVEL OF EVIDENCE: IV.

The effect of extracorporeal shock-wave therapy on pain in patients with various tendinopathies: a systematic review and meta-analysis of randomized control trials.

OBJECTIVES: Tendinopathy is a common condition that affects the body's tendon structures, causing discomfort, restricted movement, and reduced functionality. In this study, we looked at how extracorporeal shock wave therapy (ESWT) affected pain levels in individuals with various forms of tendinopathy around the world. DESIGN: This study is a comprehensive review and meta-analysis of previously published randomized controlled trials. To gather relevant data, the researchers performed keyword searches in international databases, including PubMed (Medline), Scopus, Web of Sciences, Cochrane Central Register of Controlled Trials (CENTRAL), Research Registers of ongoing trials (ClinicalTrials.gov), as well as Embase. The search was conducted up until March 2023. The quality of the selected articles was assessed using the Cochrane risk-of-bias method for randomized trials (RoB2). RESULTS: Based on the results of the meta-analysis, which included 45 clinical studies, the use of ESWT was found to have a significant impact on reducing pain in various conditions. The standardized mean difference (SMD) in patients with plantar fasciitis (PF) was reduced by 1.63 (SMD: -1.63, 95% CI: -3.04, -0.21; I2: 77.36%; P heterogeneity: 0.0001). For lateral epicondylitis (LE), the SMD was 0.63 (SMD: -0.63, 95% CI: -1.11, -0.16; I2: 67.50%; P heterogeneity: 0.003). In the case of chronic Achilles tendinopathy, the SMD was 1.38 (SMD: -1.38, 95% CI: -1.66, -1.10; I2: 96.44%; P heterogeneity: 0.0001). Additionally, in individuals with rotator cuff tendinopathy, the SMD for pain reduction was 2.37 units (SMD: -2.37, 95% CI: -3.58, -1.15; I2: 98.46%; P heterogeneity: 0.0001). CONCLUSION: This study suggests that ESWT can be a highly effective therapy option for relieving pain in people with tendinopathy. Nonetheless, it is encouraged to make additional recommendations based on high-quality clinical research and more accurate information in order to define the optimal therapeutic options for each type of tendinopathy.

Efficacy of ultrasound-guided galvanic electrolysis technique and physical therapy in patients with Achilles' tendinopathy: A pilot randomised controlled trial.

BACKGROUND: Ultrasound-guided galvanic electrolysis technique (USGET) is an innovative mini-invasive intervention with the potential to optimise outcomes in the treatment of Achille's tendinopathy (AT). OBJECTIVE: The aim of this pilot study is to evaluate the efficacy of adding USGET to conventional eccentric exercise treatment in patients with chronic AT. METHODS: Inclusion criteria were patients with unilateral non-insertional AT, pain lasting > 3 months, aged 25-60 years. Patients were randomised in two groups receiving the same physiotherapy treatment (2 sessions per week for 8 weeks). In addition, the experimental group received three USGET stimulations, one every 15 days. Outcome measures were assessment of Achilles tendinopathy severity using the Victorian Institute of Sport Assessment-Achilles (VISA-A) and pain intensity using the Visual Analogue Scale (VAS). Assessment points occurred at the onset of treatment (T0), its conclusion (T1), and subsequent follow-ups at one (T2) and two months (T3). RESULTS: Out of the 52 patients who met the study inclusion criteria, two participants withdrew from the study, resulting in a total of 50 subjects who completed the research. None of the parameters showed a different distribution at T1 (p> 0.337). At T2, there was a statistical difference in VISA-A (p= 0.010) and its subscales and VAS (p= 0.002) in the USGET group. At T3, both groups improved with a statistical difference observed in VISA-A (p< 0.001) and its subscales Pain (p= 0.004), Function (p= 0.003) and Sport (p= 0.002), but the EG patients showed a greater improvement. No adverse events were reported. CONCLUSION: The effect of USGET combined with eccentric exercise appears to be a safe and effective technique for achieving pain relief and functional recovery in the medium term, supporting the integrated use of USGET as a rehabilitative treatment option for patients with chronic AT.

Current Status and Advancements in Platelet-Rich Plasma Therapy.

Platelet-rich plasma (PRP) as a treatment modality has been around for the last four decades, but only truly gained popularity over the last 10 to 15 years in medicine, in a variety of fields ranging from regenerative medicine to infertility treatment. It has gained popularity, especially in treating musculoskeletal conditions where the bulk of research has been performed and published. There is level I evidence available supporting its efficacy in the treatment of osteoarthritis (OA), epicondylitis, bursitis, compressive neuropathy, plantar fasciitis, muscular injuries and osteochondral lesions. Most published research with regards to PRP has been focused on knee OA (limited research in shoulder, elbow, and foot and ankle OA), lateral epicondylitis and carpal tunnel syndrome, whereas spinal and hand conditions have limited research available. Tendinopathies and partial tendon tears have conflicting evidence available, with level I evidence supporting PRP's use in rotator cuff tendinopathies and tears, with contradictory level I evidence discouraging its use in patella and Achilles tendinopathies and tears. The available evidence regarding the use of PRP continues to produce conflicting results, but despite this, there is an ongoing increase in the popularity and use of PRP in patients with musculoskeletal conditions.

Karyopherins in the Remodeling of Extracellular Matrix: Implications in Tendon Injury.

Rotator Cuff Tendinopathies (RCT) are debilitating conditions characterized by alterations in the extracellular matrix (ECM) of the shoulder tendon, resulting in pain, discomfort, and functional limitations. Specific mediators, including HIF-1α, TGF-ß, MMP-9 and others have been implicated in the morphological changes observed in the tendon ECM. These mediators rely on karyopherins, a family of nuclear proteins involved in nucleo-cytoplasmic transport; however, the role of karyopherins in RCT remains understudied despite their potential role in nuclear transport mechanisms. Also, the understanding regarding the precise contributions of karyopherins in RCT holds great promise for deciphering the underlying pathophysiological mechanisms of the disease and potentially fostering the development of targeted therapeutic strategies. This article critically discusses the implications, possibilities, and perspectives of karyopherins in the pathophysiology of RCT.

Endotenon-Derived Type II Tendon Stem Cells Have Enhanced Proliferative and Tenogenic Potential.

Tendon injuries caused by overuse or age-related deterioration are frequent. Incomplete knowledge of somatic tendon cell biology and their progenitors has hindered interventions for the effective repair of injured tendons. Here, we sought to compare and contrast distinct tendon-derived cell populations: type I and II tendon stem cells (TSCs) and tenocytes (TNCs). Porcine type I and II TSCs were isolated via the enzymatic digestion of distinct membranes (paratenon and endotenon, respectively), while tenocytes were isolated through an explant method. Resultant cell populations were characterized by morphology, differentiation, molecular, flow cytometry, and immunofluorescence analysis. Cells were isolated, cultured, and evaluated in two alternate oxygen concentrations (physiological (2%) and air (21%)) to determine the role of oxygen in cell biology determination within this relatively avascular tissue. The different cell populations demonstrated distinct proliferative potential, morphology, and transcript levels (both for tenogenic and stem cell markers). In contrast, all tendon-derived cell populations displayed multipotent differentiation potential and immunophenotypes (positive for CD90 and CD44). Type II TSCs emerged as the most promising tendon-derived cell population for expansion, given their enhanced proliferative potential, multipotency, and maintenance of a tenogenic profile at early and late passage. Moreover, in all cases, physoxia promoted the enhanced proliferation and maintenance of a tenogenic profile. These observations help shed light on the biological mechanisms of tendon cells, with the potential to aid in the development of novel therapeutic approaches for tendon disorders.

Bisphosphonates-related tendinopathies and ligament disorders: Cases analysis from the U.S. Food and Drug Administration adverse event reporting system.

Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such adverse reactions result from the use of bisphosphonates (BPs). In this study, we assessed the correlation between TPLDs and the use of BPs via U.S. FDA Adverse Event Reporting System (FAERS) database. Bayesian and nonproportional analyses were applied to data retrieved from the FAERS database from the first quarter of 2004 to the third quarter of 2022. A total of 3202 reported cases of TPLDs were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, zoledronate), with statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Alendronate showed the highest association with tendinopathies and ligament disorders (ROR = 16.30, PRR = 15.47, IC = 3.88), while zoledronate had the lowest association (ROR = 2.13, PRR = 2.12, IC = 1.08), which was consistent with the results of top 10 preferred terms (PTs) under the narrow standardized MedDRA queries (SMQs) sorted by frequency of reports. Excluding zoledronate, over half of patients who reported BP-related TPLDs were hospitalized, either briefly or extendedly. This was especially true for alendronate, which showed the highest rate of hospitalization (83.25 %), however, the mortality rate reported by those taking alendronate were significantly lower than those of zoledronate and pamidronate. In addition, the clinical characteristics of BP-related TPLDs was analyzed. It is more common to reported in middle-aged and elderly females, the highest proportion was in 50-69 years old. Except for osteoporosis, osteopenia, and osteoporosis prophylaxis, cancer bone metastasis was also the indication of some BPs. The most often reported concomitant/prior medicines were calcium supplements, another BPs, antitumor agents, and nonsteroidal anti-inflammatory drugs. In conclusion, we provide a comprehensive overview of the correlation and clinical characteristics, and prognosis of BP-related TPLDs deserving continued surveillance and appropriate management.

Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital.

Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite for sound and homogeneous clinical efficacy evaluation. This retrospective study (2013-2020) considered the standardized GMP manufacturing and sports medicine-related clinical use of autologous PRP for tendinopathies at the Lausanne University Hospital (Lausanne, Switzerland). This study included 48 patients (18-86 years of age, with a mean age of 43.4 years, and various physical activity levels), and the related PRP manufacturing records indicated a platelet concentration factor most frequently in the range of 2.0-2.5. The clinical follow-up showed that 61% of the patients reported favorable efficacy outcomes (full return to activity, with pain disappearance) following a single ultrasound-guided autologous PRP injection, whereas 36% of the patients required two PRP injections. No significant relationship was found between platelet concentration factor values in PRP preparations and clinical efficacy endpoints of the intervention. The results were in line with published reports on tendinopathy management in sports medicine, wherein the efficacy of low-concentration orthobiologic interventions appears to be unrelated to sport activity levels or to patient age and gender. Overall, this study confirmed the effectiveness of standardized autologous PRP preparations for tendinopathies in sports medicine. The results were discussed in light of the critical importance of protocol standardization for both PRP manufacturing and clinical administration to reduce biological material variability (platelet concentrations) and to enhance the robustness of clinical interventions (comparability of efficacy/patient improvement).

Ultrasound Morphometry and Mean Echogenicity of Digital Flexor Tendons, Suspensory Ligament, and Accessory Ligament of Digital Deep Flexor Tendon in Gaited Horses.

The objective of this study was to evaluate and compare the sonographic characteristics of the digital flexor tendons and ligaments of the palmar/plantar of the metacarpal and metatarsal regions in gaited horses, as well as to establish normal reference ultrasound values for Mangalarga Marchador (MM) and Campeiro breeds. Transverse sonographic images were obtained of 50 adult and healthy horses from the MM (n = 25) and Campeiro (n = 25) breeds. The images were taken in six metacarpal/metatarsal zones, and the following measurements were taken: transverse area, circumference, dorsopalmar/plantar length, lateromedial length, and mean echogenicity. Differences were observed between breeds in the fore- and hindlimbs, and, even when not significant, the Campeiro breed tended to have higher values for most variables and structures. Variations between zones and between structures in the same zone followed a similar trend in both breeds for all variables. In addition, the dimensions and variations between zones and structures were different between the fore- and hindlimbs, highlighting the need for specific values for the digital flexor tendons and ligaments of the metatarsal plantar region. In conclusion, the digital flexor tendons, suspensory ligaments, and accessory ligaments of the digital deep flexor tendon are influenced by the breed factor in gaited horses, and they are different between the fore- and hindlimbs.

Prospects of magnetically based approaches addressing inflammation in tendon tissues.

Tendon afflictions constitute a significant share of musculoskeletal diseases and represent a primary cause of incapacity worldwide. Unresolved/chronic inflammatory states have been associated with the onset and progression of tendon disorders, contributing to undesirable immune stimulation and detrimental tissue effects. Thus, targeting persistent inflammatory events could assist important developments to solve pathophysiological processes and innovative therapeutics to address impaired healing and accomplish complete tendon regeneration. This review overviews the impact of inflammation and inflammatory mediators in tendon niches, unveiling the importance of tendon cell populations and their signature features, and the influence of microenvironmental factors on inflamed and injured tendons. The demand for non-invasive instructive strategies to manage persistent inflammatory mediators, guide inflammatory pathways, and modulate cellular responses will also be approached by exploring the role of pulsed electromagnetic field (PEMF). PEMF alone or combined with more sophisticated systems triggered by magnetic fields will be considered in the design of successful therapies to control inflammation in tendinopathic conditions.

Polydeoxyribonucleotide in the Treatment of Tendon Disorders, from Basic Science to Clinical Practice: A Systematic Review.

Polydeoxyribonucleotide (PDRN) is a proprietary and registered drug with several beneficial effects, including tissue repairing, anti-ischemic action, and anti-inflammatory properties. The present study aims to summarize the current evidence about PRDN's clinical effectiveness in the management of tendon disorders. From January 2015 to November 2022, OVID-MEDLINE®, EMBASE, Cochrane Library, SCOPUS, Web of Science, Google Scholar and PubMed were searched to identify relevant studies. The methodological quality of the studies was evaluated, and relevant data were extracted. Nine studies (two in vivo studies and seven clinical studies) were finally included in this systematic review. Overall, 169 patients (male: 103) were included in the present study. The effectiveness and safeness of PDRN has been investigated in the management of the following diseases: plantar fasciitis; epicondylitis; Achilles tendinopathy; pes anserine bursitis; chronic rotator cuff disease. No adverse effects have been recorded in the included studies and all the patients showed an improvement in clinical symptoms during the follow-up. PDRN are a valid emerging therapeutic drug in the treatment of tendinopathies. Further multicentric randomized clinical studies are needed to better define the therapeutic role of PDRN, especially in combined clinical protocols.

The roles and therapeutic potentialof mesenchymal stem/stromal cells and their extracellular vesicles in tendinopathies.

Tendinopathies encompass a highly prevalent, multi-faceted spectrum of disorders, characterized by activity-related pain, compromised function, and propensity for an extended absence from sport and the workplace. The pathophysiology of tendinopathy continues to evolve. For decades, it has been related primarily to repetitive overload trauma but more recently, the onset of tendinopathy has been attributed to the tissue's failed attempt to heal after subclinical inflammatory and immune challenges (failed healing model). Conventional tendinopathy management produces only short-term symptomatic relief and often results in incomplete repair or healing leading to compromised tendon function. For this reason, there has been increased effort to develop therapeutics to overcome the tissue's failed healing response by targeting the cellular metaplasia and pro-inflammatory extra-cellular environment. On this basis, stem cell-based therapies have been proposed as an alternative therapeutic approach designed to modify the course of the various tendon pathologies. Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells often referred to as "medicinal signaling cells" due to their immunomodulatory and anti-inflammatory properties that can produce a pro-regenerative microenvironment in pathological tendons. However, the adoption of MSCs into clinical practice has been limited by FDA regulations and perceived risk of adverse events upon infusion in vivo. The introduction of cell-free approaches, such as the extracellular vesicles of MSCs, has encouraged new perspectives for the treatment of tendinopathies, showing promising short-term results. In this article, we review the most recent advances in MSC-based and MSC-derived therapies for tendinopathies. Preclinical and clinical studies are included with comment on future directions of this rapidly developing therapeutic modality, including the importance of understanding tissue loading and its relationship to any treatment regimen.

The Co-Use of Stromal Vascular Fraction and Bone Marrow Concentrate for Tendon Healing.

OBJECTIVE: The Achilles tendon is the most frequently injured tendon in the human body, despite being the strongest. Many conventional treatments including medication, surgical interventions, and physical therapy are available, however, the desired results are often not achieved. Stromal vascular fraction (SVF) and bone marrow concentrate (BMC) are two additional cellular treatment options. The purpose of this study is to evaluate the effect of SVF and BMC, used as a combination, for the treatment of Achilles tendon injuries. METHODS: Five male New Zealand rabbits were used for each of the 6 study groups. A 3-mm of SVF and BMC were injected on the Achilles tendons at certain ratios. The histological results were classified by the Movin grading system for tendon healing. The collagen type-I and type-III structures in the tendons were examined by immunohistochemical evaluation. The expressions of tendon-specific genes were also examined by using the RT-PCR method to analyze tendon healing. RESULTS: Histological and immunohistochemical evaluation indicated that tendons receiving the SVF and BMAC mixture performed better than control and individual groups (p < 0.05). Moreover, RT-PCR evaluation showed that mixture-receiving groups were the closest similar to the uninjured group (p < 0.05). CONCLUSION: The combined use of BMC and SVF improved Achilles tendon healing when compared to the individual use of each mixture.

Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review.

Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.

Lyophilized Progenitor Tenocyte Extracts: Sterilizable Cytotherapeutic Derivatives with Antioxidant Properties and Hyaluronan Hydrogel Functionalization Effects.

Cultured primary progenitor tenocytes in lyophilized form were previously shown to possess intrinsic antioxidant properties and hyaluronan-based hydrogel viscosity-modulating effects in vitro. The aim of this study was to prepare and functionally characterize several stabilized (lyophilized) cell-free progenitor tenocyte extracts for inclusion in cytotherapy-inspired complex injectable preparations. Fractionation and sterilization methods were included in specific biotechnological manufacturing workflows of such extracts. Comparative and functional-oriented characterizations of the various extracts were performed using several orthogonal descriptive, colorimetric, rheological, mechanical, and proteomic readouts. Specifically, an optimal sugar-based (saccharose/dextran) excipient formula was retained to produce sterilizable cytotherapeutic derivatives with appropriate functions. It was shown that extracts containing soluble cell-derived fractions possessed conserved and significant antioxidant properties (TEAC) compared to the freshly harvested cellular starting materials. Progenitor tenocyte extracts submitted to sub-micron filtration (0.22 µm) and 60Co gamma irradiation terminal sterilization (5−50 kGy) were shown to retain significant antioxidant properties and hyaluronan-based hydrogel viscosity modulating effects. Hydrogel combination products displayed important efficacy-related characteristics (friction modulation, tendon bioadhesivity) with significant (p < 0.05) protective effects of the cellular extracts in oxidative environments. Overall, the present study sets forth robust control methodologies (antioxidant assays, H2O2-challenged rheological setups) for stabilized cell-free progenitor tenocyte extracts. Importantly, it was shown that highly sensitive phases of cytotherapeutic derivative manufacturing process development (purification, terminal sterilization) allowed for the conservation of critical biological extract attributes.

Implantable medical devices for tendon and ligament repair: a review of patents and commercial products.

INTRODUCTION: Tendon and ligament injuries are a frequent and debilitating issue that affects many patients worldwide. The predominant solution is the suture thread, which is not without potential side effects and limitations. Implantable medical devices have gained more attention as an alternative approach. However, due to the many challenges of the inner body environment (limited available space, chemically aggressive environment, etc), the development of suitable devices is not exempt from practical and technical difficulties. AREAS COVERED: Here, implantable medical devices for tendon and ligaments injuries are reviewed and discussed. Commercially-available products and registered patents are all considered as long as they fit the standard definitions of 'implantable medical devices' (reported in the Introduction). The research was then narrowed down to five commercial products, deemed as the most representative of the whole market. Their effectiveness and performance are analysed, as well as the possible areas of improvement and development. EXPERT OPINION: Commercially available products present overall superior mechanical performances than suture techniques. Nevertheless, these latter ones might be still preferred for their wider range of customization. This aspect, and many others, could represent an area of improvement for implantable medical devices, to further explore their potential for tendon and ligament repair.

Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review.

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs.

Quantitative shear wave elastography compared to standard ultrasound (qualitative B-mode grayscale sonography and quantitative power Doppler) for evaluation of achillotendinopathy in treatment-naïve individuals: A cross-sectional study.

BACKGROUND: Achillotendinopathy is reported as an overuse disorder and/or degeneration change of the tendon. The diagnosis of tendinopathy is not always easy through imaging modalities. The B-mode grayscale sonography and power Doppler are well-established methods aimed at visualising tendon structure, but have limited sensitivity and lack conventional sonographic characteristics in symptomatic patients. Shear wave ultrasound elastography quantitatively assesses tissue stiffness. OBJECTIVES: To compare the diagnostic accuracy of shear wave ultrasound elastography to that of standard ultrasound (combined B-mode grayscale sonography and power Doppler) for diagnosis of achillotendinopathy, considering clinical symptoms as the reference standard. MATERIAL AND METHODS: Standard questionnaires regarding medical history and the Chinese version of a Victorian Institute of Sports Assessment - Achilles Questionnaires (VISA-AC) score were evaluated for a total of 14 treatment-naïve patients with complaints of localized swelling, and reduced force and/or flexibility of the Achilles tendon(s). The irregular thickening around the Achilles tendon, heterogeneity of echotexture of the tendon and calcification of the calcaneal attachment were considered incidences of tendinopathy in B-mode grayscale sonography. Tendinopathies were considered if tendons were >0.60 cm thick in power Doppler. Shear wave elasticity <350 kpa (10 m/s) was considered tendinopathy. RESULTS: A total of 28 conditions of both sides were evaluated through standard ultrasound examinations. Eighty-four tendons were assessed using shear wave ultrasound elastography. Asymptomatic tendons were visible as red and symptomatic (VISA-AC score <80) tendons were visible as blue or turquoise in the images. The rigidity of symptomatic tendons was lower than that of asymptomatic tendons (p < 0.0001). Sensitivity and accuracy for standard ultrasound were increased by the addition of shear wave ultrasound elastography for both symptomatic and asymptomatic tendons. The VISA-AC score was strongly correlated with the elasticity values (p = 0.000, Kendall's tau-beta (τß) = 0.71) of Achilles tendons. CONCLUSIONS: Shear wave ultrasound elastography augments diagnostic confidence of standard ultrasound for the treatment of tendinopathies of Achilles tendons.

Tendon Immune Regeneration: Insights on the Synergetic Role of Stem and Immune Cells during Tendon Regeneration.

Tendon disorders represent a very common pathology in today's population, and tendinopathies that account 30% of tendon-related injuries, affect yearly millions of people which in turn cause huge socioeconomic and health repercussions worldwide. Inflammation plays a prominent role in the development of tendon pathologies, and advances in understanding the underlying mechanisms during the inflammatory state have provided additional insights into its potential role in tendon disorders. Different cell compartments, in combination with secreted immune modulators, have shown to control and modulate the inflammatory response during tendinopathies. Stromal compartment represented by tenocytes has shown to display an important role in orchestrating the inflammatory response during tendon injuries due to the interplay they exhibit with the immune-sensing and infiltrating compartments, which belong to resident and recruited immune cells. The use of stem cells or their derived secretomes within the regenerative medicine field might represent synergic new therapeutical approaches that can be used to tune the reaction of immune cells within the damaged tissues. To this end, promising opportunities are headed to the stimulation of macrophages polarization towards anti-inflammatory phenotype together with the recruitment of stem cells, that possess immunomodulatory properties, able to infiltrate within the damaged tissues and improve tendinopathies resolution. Indeed, the comprehension of the interactions between tenocytes or stem cells with the immune cells might considerably modulate the immune reaction solving hence the inflammatory response and preventing fibrotic tissue formation. The purpose of this review is to compare the roles of distinct cell compartments during tendon homeostasis and injury. Furthermore, the role of immune cells in this field, as well as their interactions with stem cells and tenocytes during tendon regeneration, will be discussed to gain insights into new ways for dealing with tendinopathies.

Efficacy of autologous mesenchymal stromal cell treatment for chronic degenerative musculoskeletal conditions in dogs: A retrospective study.

Introduction: The objective of this study was to retrospectively analyze clinical data from a referral regenerative medicine practice, to investigate the efficacy of autologous mesenchymal stromal cells (MSC) in 245 dogs deemed unresponsive to conventional treatment by their referring vet. Methods: Diagnostic imaging [radiology and musculoskeletal ultrasound (MSK-US)] identified musculoskeletal pathology holistically. MSCs, produced according to current guidelines, were initially administered with PRP by targeted injection to joints and/or tendons, with a second MSC monotherapy administered 12 weeks later to dogs with severe pathology and/or previous elbow arthroscopic interventions. Dogs with lumbosacral disease received epidural MSCs with additional intravenous MSCs administered to dogs with spondylosis of the cervical, thoracic and lumbar spine. All dogs received laser therapy at 10 J/cm2 at the time of treatment and for 5 sessions thereafter. Objective outcome measures (stance analysis, range of joint motion, pressure algometry) and validated subjective outcome measures (owner reported VetMetrica HRQL™ and veterinary pain and quality of life impact scores) were used to investigate short and long-term (6-104 weeks) efficacy. Outcome data were collected at predetermined time windows (0-6, 7-12, 13-18, 19-24, 25-48, 49-78, 79-104) weeks after initial treatment. Results: There were statistically significant improvements in post compared with pre-treatment measures at all time windows in stance analysis, shoulder and hip range of motion, lumbosacral pressure algometry, and to 49-78 weeks in carpus and elbow range of motion. Improvements in 4 domains of quality of life as measured by VetMetricaTM were statistically significant, as were scores in vet-assessed pain and quality of life impact. In dogs receiving one initial treatment the mean time before a second treatment was required to maintain improvements in objective measures was 451 days. Diagnostic imaging confirmed the regenerative effects of MSCs in tendinopathies by demonstrating resolution of abnormal mineralization and restoration of normal fiber patterns. Discussion: This represents the first study using "real-world" data to show that cell-based therapies, injected into multiple areas of musculoskeletal pathology in a targeted holistic approach, resulted in rapid and profound positive effects on the patient's pain state and quality of life which was maintained with repeat treatment for up to 2 years.