Adipose Stem Cell–Derived Exosomes Recover Impaired Matrix Metabolism of Torn Human Rotator Cuff Tendons by Maintaining Tissue Homeostasis

Background: Adipose stem cell–derived exosomes (ASC-Exos) are reported to effectively prevent muscle atrophy and degeneration of torn rat rotator cuff, but their influence on human samples and their potential mechanism are still unclear. Purpose: We aimed to investigate the effects of ASC-Exos on the metabolic activities of torn human rotator cuff tendons and explore the potential mechanism behind it. Study Design: Controlled laboratory study. Methods: Diseased supraspinatus tendons were harvested from 15 patients with a mean ± SD age of 65.8 ± 3.2 years who underwent reverse shoulder arthroplasty for chronic rotator cuff tears associated with glenohumeral pathological changes. Each tendon was dissected into 3 × 4 × 4–mm explants: the ones derived from the same tendon were placed into 12-well plates and cultured in complete culture media (control) or in complete culture media supplemented with ASC-Exos for 72 hours. Afterward, the concentrations of cytokines secreted into the culture media—including interleukin 1β (IL-1β), IL-6, IL-8, and matrix metalloproteinase 9 (MMP-9)—were measured using enzyme-linked immunosorbent assay (ELISA). Tendons were stained with hematoxylin and eosin and immunohistochemistry (type I and III collagens) for histological analyses. Moreover, the expression of anabolic genes ( TIMP-1 and TIMP-3; type I and III collagen encoding) and catabolic genes ( MMP-9 and MMP-13) in tendons were measured using real-time quantitative polymerase chain reaction. Phosphorylated AMPKα and Wnt/β-catenin pathways were assayed by western blotting to explore the potential mechanism of action of ASC-Exos. Results: Secretion of proinflammatory cytokines, including IL-1β, IL-6, and MMP-9, was significantly reduced in the ASC-Exos group as compared with the control group. Supraspinatus tendons in the ASC-Exos group exhibited superior histological properties, as demonstrated by higher tendon maturing scores and more type I collagen content, but there was no significant difference in type III collagen content between groups. Expression of MMP-9 and MMP-13 genes was decreased in the ASC-Exos group versus the control group. Increased expression of type I and III collagens and an elevated type I/III ratio were found in the ASC-Exos group when compared with the control group. There was no significant difference in the secretion of IL-8 and expression of TIMP-1 and TIMP-3 genes between the ASC-Exos and control groups. Western blotting revealed that ASC-Exos enhanced phosphorylated AMPKα and decreased β-catenin levels to prevent tendon degeneration. Conclusion: ASC-Exos maintained metabolic homeostasis of torn human rotator cuff tendons to improve their histological properties, which might be achieved by enhancing AMPK signaling to suppress Wnt/β-catenin activity. Clinical Relevance: ASC-Exos could be used as an effective biological tool to promote healing in torn human rotator cuff tendons.

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The influence of the Kinesio Taping on selected ultrasonography measurements, and quality of life in patients with rotator cuff lesions

Scientific Reports ◽

10.1038/s41598-020-75701-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Aneta Bac ◽

Magdalena Wróbel ◽

Katarzyna Ogrodzka-Ciechanowicz ◽

Edyta Michalik ◽

Anna Ścisłowska-Czarnecka

Keyword(s):

Quality Of Life ◽

Rotator Cuff ◽

Statistical Significance ◽

Control Group ◽

Subacromial Space ◽

Kinesio Taping ◽

Significant Difference ◽

Rotator Cuff Lesions ◽

Significant Change

Abstract The assessment of the six-week influence of Kinesio Taping combined with a rehabilitation on selected ultrasonography measurements, the level of disability, and the quality of life in patients with rotator cuff lesions. 60 participants were randomly assigned into a taping group (KT combined with a six-week rehabilitating protocol) and a control group (only rehabilitation protocol). In all patients the following assessments were performed twice: USG, UEFI and NHP questionnaires. In the examination of the subacromial space and the subacromial bursa in the taping group, no statistical significance was observed. A statistically significant change in the thickness of the muscles was obtained only for the thickness of the infraspinatus in the taping group. A statistically significant change was obtained in the assessment of tendinopathy only for the supraspinatus muscle in both groups. Within both groups a statistically significant difference was observed in the average UEFI and NHP scores; however, the differences in the scores obtained between the groups were not statistically significant. The use of KT with a rehabilitation program did not yield statistically significantly better results in the improvement of selected shoulder region indicators, the function of the upper limb and the quality of life.

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Latihan Fisik Intesitas Submaksimal dan Kalsitonin Salmon Meningkatkan Kepadatan Tulang Tikus Masa Pertumbuhan

10.31227/osf.io/35sfn ◽

2018 ◽

Author(s):

Heru Syarli Lesmana ◽

Gadis Meinar Sari ◽

Choesnan Effendi ◽

Shinta Arisant

Keyword(s):

Bone Density ◽

Salmon Calcitonin ◽

Bone Matrix ◽

Growth Period ◽

Control Group ◽

P Value ◽

Type I ◽

Femur Bone ◽

Risk Increase ◽

Significant Difference

Bone is a complex tissue consisting of cells and matrix. Mass and thick bone mass has a dynamic addition and subtraction through the process of remodeling (bone matrix absorbed and formed again). Bone is formatted by osteoblast cell and resorption by osteoclast cell. Osteoblasts produce a matrix of osteoid, which is composed mainly of type I collagen, and osteoclast removes bone tissue by removing its mineralized matrix and breaking up the organic bone. Bone remodeling purpose to defend shape and structure of bone. the purpose of this study is to prove that submaximal-intensity exercise and salmon calcitonin improve bone density in growing rat this research method uses design of the randomize posttest only control group design. We compered femur bone density in 24 male norvegicus rats aged 6 weeks that were divided into 4 groups: controls, calcitonin, exercise, combine. Exercise group swam 3 times a week in submaximal intensity, calcitonin group injected synthetic salmon calcitonin 2 iu /100 gram of rat weight every day and combine group did both of it. After 8 weeks, rat femur bone density measured using ultrasound. the result: there are significant differences in bone density between group 1 (control) and group 4 (combine) with p = 0.001, thus the p value <0.05 indicates that there is a significant difference to the average density in both groups. While comparisons to other groups found no significant difference because the value of p> 0.05. the benefits of this research are calcitonin salmon and submaximal-intensity exercise increase the density bone in the growth period. High bone density is mean the bone is strong and health, not porous and fragile so decrease bone fracture risk. increase the bone density in of growth period make the bone get the best mass, and avoid from early osteoporosis.

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Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds

10.1101/436444 ◽

2018 ◽

Author(s):

Yasuhiko Kaita ◽

Takehiko Tarui ◽

Hideaki Yoshino ◽

Takeaki Matsuda ◽

Yoshihiro Yamaguchi ◽

...

Keyword(s):

Wound Healing ◽

Therapeutic Effect ◽

Healing Process ◽

Control Group ◽

Type I ◽

Burn Wound ◽

Burn Wounds ◽

Burn Wound Healing ◽

Significant Difference ◽

Regenerative Cells

AbstractThe purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs.Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses.In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs.These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings.

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Cellular Compatibility of a New Tantalum-Niobium Scaffold Material

10.21203/rs.3.rs-39637/v1 ◽

2020 ◽

Author(s):

Jianan Ouyang ◽

Zhenhan Deng ◽

Kang Chen ◽

Jianyi Xiong ◽

Ying Li ◽

...

Keyword(s):

Cell Proliferation ◽

Type I Collagen ◽

Material Surface ◽

Control Group ◽

Type I ◽

Scaffold Material ◽

Rt Pcr ◽

Pcr Assay ◽

Porous Tantalum ◽

Significant Difference

Abstract [Objective] To determine the cellular compatibility of porous tantalum-niobium (Ta-Nb) material. [Method] Rabbit osteoblasts were co-cultured with porous Ta-Nb material. The cell proliferation was detected by CCK-8 method, and the cell adhesion was observed under scanning electron microscope (SEM). The expressions of type-I collagen and osteocalcin were detected by RT-PCR assay. [Results] CCK-8 detection indicated that the cell proliferation on the porous Ta-Nb material showed no difference from that of the control group (P>0.05). SEM revealed that a large amount of cells adhered onto the surface and in the pores of the material. The number of cells on the material surface increased obviously over time. RT-PCR assay showed that with the prolonging of the time of co-culture, the expression of type-I collagen was enhanced (P<0.05), while the osteocalcin expression exhibited no significant difference (P>0.05[Conclusion] Porous Ta-Nb scaffold material can be used to promote the adhesion, growth and differentiation of osteoblasts with satisfactory cellular compatibility.

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Peri-implantitis and extracellular matrix antibodies: A case–control study

European Journal of Dentistry ◽

10.4103/ejd.ejd_28_17 ◽

2017 ◽

Vol 11 (03) ◽

pp. 340-344 ◽

Cited By ~ 5

Author(s):

Piero Papi ◽

Stefano Di Carlo ◽

Daniele Rosella ◽

Francesca De Angelis ◽

Mario Capogreco ◽

...

Keyword(s):

Extracellular Matrix ◽

Case Control Study ◽

Test Group ◽

Case Control ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Fisher Exact Test ◽

Type I ◽

Significant Difference ◽

Control Study

ABSTRACT Objective: The aim of this case–control study was to compare patients with a healthy peri-implant environment and patients affected by peri-implantitis, evaluating the occurrence of antibodies to extracellular matrix (ECM) molecules. The authors hypothesized the presence of ECM autoantibodies in serum of peri-implantitis patients. Materials and Methods: Patients were divided into two groups: one with dental implants with a diagnosis of peri-implantitis and one control group with implants classified as being “healthy.” Enzyme-linked immunosorbent assay was performed on patients' sera to detect human antibodies to type I, III, IV, and V collagens, laminin, and fibronectin. Fisher exact test was performed to evaluate statistical association, with a significant P < 0.05. Results: Forty-two patients were enrolled in this study, 27 females (64.28%) and 15 males (35.72%) with a mean age of 53 ± 29.69 years (age range 32–74). The presence of antibodies to CIII was recorded in 6/21 (28.57%) patients of test group, compared to just 2/21 (9.52%) for the control group, showing a statistically significant difference (P < 0.05). Other antibodies tested were found to be not statistically significant or absent. Conclusions: Within the limitations of this study, it can be concluded that further studies, with larger sample and different design, are necessary to address the research purpose, evaluating possible associations between anti-ECM antibodies and peri-implantitis.

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Could superior capsule findings be used as a predictor for partial bursal-sided rotator cuff tears?

Journal of Orthopaedic Surgery ◽

10.1177/2309499019895153 ◽

2020 ◽

Vol 28 (1) ◽

pp. 230949901989515 ◽

Cited By ~ 1

Author(s):

Ulunay Kanatlı ◽

Tacettin Ayanoglu ◽

Erdinc Esen ◽

Baybars Ataoglu ◽

Mustafa Ozer ◽

...

Keyword(s):

Rotator Cuff ◽

Glenohumeral Joint ◽

Arthroscopic Treatment ◽

Rotator Cuff Tears ◽

Subacromial Impingement Syndrome ◽

Control Group ◽

Study Group ◽

Coracoacromial Ligament ◽

Cuff Tear ◽

Significant Difference

Purpose: The purpose of this study was to investigate the relationship between the superior capsule tear patterns and synovitis with subacromial pathologies, such as bursal-sided rotator cuff tear and subacromial impingement syndrome. Methods: Fifty patients who underwent arthroscopic treatment for isolated bursal-sided tear were included in the study. Fifty more patients who underwent arthroscopic treatment for isolated Superior Labrum Anterior Posterior (SLAP) 2 lesion without pathology in the rotator cuff were included in the control group. Firstly, superior capsule tear and common synovitis on the rotator cable were assessed during glenohumeral joint examination. Coracoacromial Ligament (CAL) degeneration grading was performed according to the Royal Berkshire Hospital classification. Bursal-sided partial tear grading was done using Ellman classification. Whether or not there was a relationship between synovitis, classic capsule tear, plus reverse flap capsule tear, and partial bursal-sided tear existence. Results: There were 21 patients with reverse flap capsule tear in the study group and 3 patients in the control group. In addition, there were 13 patients with synovitis in the study group and 4 in the control group. Compared to the control group, there was also a significant positive correlation in the presence of both synovitis and reverse flap capsule tear with the presence of bursal-sided tear in the study group ( p = 0.000). There was, however, no significant difference between the presence of classical capsule tear and the presence of bursal-sided tear ( p = 0.485). Conclusion: This study shows that the presence of reverse flap capsule tear and synovitis was associated with partial bursal-sided tears. Therefore, if the reverse flap capsule tear or synovitis is detected in the superior capsule, the rotator cuff should be evaluated in more detail during subacromial bursoscopy in order not to miss a bursal-sided partial cuff tear.

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Evaluation of tendinosis of the long head of the biceps tendon by strain and shear wave elastography

Medical Ultrasonography ◽

10.11152/mu-1323 ◽

2018 ◽

Vol 20 (2) ◽

pp. 192 ◽

Cited By ~ 5

Author(s):

Mehmet Hamdi Sahan ◽

Mikail Inal ◽

Veysel Burulday ◽

Turgut Kultur

Keyword(s):

Shear Wave ◽

Biceps Tendon ◽

Shear Wave Elastography ◽

Tissue Type ◽

Diagnostic Tools ◽

Control Group ◽

Type I ◽

Color Mapping ◽

Significant Difference ◽

Long Head

Aim: To investigate strain (SE) and shear wave elastography (SWE) characteristics of the long head of the biceps tendon (LHBT) tendinosis in comparison with magnetic resonance imaging (MRI) findings.Material and methods: Twenty patients with a MRI diagnosis of tendinosis and twenty healthy subjects with normal LHBT in MRI were prospectively examined by SE and SWE. SE color mapping was divided into four types in accordance with elasticity designs: type I predominantly blue (hardest tissue), type II predominantly blue-green (hard tissue), type III predominantly green (intermediate tissue), type IV predominantly green-yellow-red (soft tissue). Quantitative measurements of LHBT hardness with SWE were analyzed in kilopascals (kPa).Results: In the tendinosis group SE types in transverse scan were I in 24% of tendons, II in 50%, III in 25%, and in longitudinal scan I in 15%, II in 75%, and III in 10%. In the control group SE types in transversescan were II in 10% of tendons, III in 55%, IV in 35%, and in longitudinal scan II in 10%, III in 55%, and IV in 35%. SWE values in transverse scan were 38.32±7.2 kPa in the tendinosis group and 18.6±3.1 kPa in the control groupand in longitudinal scan 39.42±7.4 kPa in the tendinosis group, and 20.62±4.6 in the control group. There was a statistically significant difference in terms of elasticity patterns between the tendinosis and control groups (p<0.001). The receiver operating characteristic curve analysis was perfect and a cut-off value of tranverse 25.8 kPa and longitudinal, 24.6 kPa shear values had very high sensitivity and specificity for tendinosis.Conclusion: SE and SWE may be useful diagnostic tools for LHBT tendinosis when considering usability, cost effectiveness, and patient preference compared to MRI.

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Prospective Clinical Research of the Efficacy of Platelet-rich Plasma in the Outpatient-based Treatment of Rotator Cuff Tendinopathy

Clinics in Shoulder and Elbow ◽

10.5397/cise.2019.22.2.61 ◽

2019 ◽

Vol 22 (2) ◽

pp. 61-69

Author(s):

Ho-Won Lee ◽

Kyung-Ho Choi ◽

Jung-Youn Kim ◽

Ik Yang ◽

Kyu-Cheol Noh

Keyword(s):

Rotator Cuff ◽

Conservative Treatment ◽

Rating Scale ◽

Platelet Rich Plasma ◽

Constant Score ◽

Statistical Significance ◽

Clinical Results ◽

Control Group ◽

Significant Difference ◽

Rotator Cuff Tendinopathy

Background: The purpose of this study is to compare the clinical outcomes of the control group and platelet-rich plasma (PRP) group among the patients who failed to respond to conservative treatment as outpatient-based therapy for rotator cuff tendinopathy, and to compare the clinical results of leukocyte-poor (LP) PRP and leukocyte-rich (LR) PRP.Methods: Inclusion criteria are (1) over 18-year-old, (2) patients with rotator cuff tendinopathy, no rotator cuff tear by radiologic diagnosis (ultrasonography or magnetic resonance imaging) within the last 3 months, and (3) not effective to conservative treatment for more than 1 month. Of the final 60 subjects, 33 patients in the exercise treatment group and 27 patients in the PRP injection group (LP-PRP, 13; LR-PRP, 14) were included. Clinical evaluation was carried out by assessing the outcomes of treatment using the Numeric Rating Scale pain score, the American Shoulder and Elbow Society (ASES) score, and the Constant score at baseline and at 3 and 6 months after the procedure.Results: There was a statistically significant difference in ΔASES3months (ASES3months-ASESfirst) score between the control and PRP groups (p=0.006). However, there was no statistical significance between LP-PRP and LR-PRP groups (p>0.05).Conclusions: This study showed that PRP injection was more effective than exercise therapy for the first 3 months. However, there was no difference between the LP-PRP group and the LR-PRP group. Regardless of the type of PRP, clinical application of PRP injection in patients with rotator cuff tendinopathy seems to be effective in early treatment.

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Stem cell application in rotator cuff repair: Interposition stem cell sheet versus overlaid stem cell sheet

10.21203/rs.3.rs-25042/v1 ◽

2020 ◽

Author(s):

Jae hee Choi ◽

Michael Seungcheol Kang ◽

Myung Jin Shin ◽

Dong Min Kim ◽

Yu Na Lee ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Rotator Cuff ◽

Rotator Cuff Repair ◽

Surgical Repair ◽

Cell Sheet ◽

Biomechanical Analysis ◽

Control Group ◽

Cell Sheets ◽

Cuff Repair

Abstract Background Stem cells are an effective method of biologic healing and can be used to enhance the natural enthesis of the tendon-to-bone junction in rotator cuff repair. The purpose of this study was to investigate if the application of engineered stem cell sheets using adipose-derived cells (ADSCs) was effective in regeneration of natural enthesis and if there was a difference in the result of repair depending on the applied location Methods A chronic rotator cuff tear model was induced for 2 weeks, and cell sheets made using ADSCs isolated from rats were transplanted into the tendon-to-bone junction during surgical repair. Depending on the transplant location of the cell sheet, the difference in rotator cuff healing level between the overlaid group and the interposition group was compared to the surgical repair only group. The samples were obtained based on the tendon-to-bone junction and analysis of gross morphology, histology staining, and biomechanical analysis were performed. Results The differentiation potentials of ADSCs as stem cells were confirmed, as was the potential for tenogenic differentiation by growth factors. ADSCs were prepared as a sheet form to maintain the shape at the target site and to be easily attached. GFP-expressing ADSCs were proliferated in vivo and observed at the transplantation site. The overall healing level was better in the cell sheet transplanted group than in the control group that surgical repair only. Additionally, differences in healing level were shown depending on the cell sheet location by morphological, histological, and biomechanical perspectives. Histological results showed that the interposition transplantation group (1.75 ± 0.43, P = 0.004) showed better fibrocartilage formation and collagen orientation at the junction than the overlaid transplantation group (0.86 ± 0.83). Conclusion In the chronic rotator cuff repair model, the engineered stem cell sheets enhanced the regeneration of the tendon-to-bone junction. This regeneration was more effective when the stem cell sheet was interpositioned at the tendon-to-bone interface. Trial registration: Not applicable

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PO-007 Association of six gene polymorphism with tendon injuries in Chinese athletes

Exercise Biochemistry Review ◽

10.14428/ebr.v1i3.8863 ◽

2018 ◽

Vol 1 (3) ◽

Author(s):

Qi Wei

Keyword(s):

Gene Polymorphism ◽

Collagen Type ◽

Sports Injury ◽

Collagen Matrix ◽

Collagen Type I ◽

Tendon Injuries ◽

Control Group ◽

Type I ◽

Polymorphic Loci ◽

Significant Difference

Objective In recent years, more and more studies have shown that gene polymorphism is associated with susceptibility and recovery of sports injury. We select Collagen type I alpha 1 gene(COL1A1 ),Collagen type V alpha 1 gene (COL5A1),Collagen type XII alpha 1 gene (COL12A1),1ollagen type XIV alpha 1 gene(COL14A1),Tenascin C gene(TNC), Growth/differentiation factor-5 gene(GDF-5) polymorphic loci to study their relationship with tendon injuries in Chinese athletes. Methods A case-control experiment was designed to analyze the distribution characteristics of six gene polymorphism loci in 65 chinese athlete injured group and 115 control group. These six polymorphic loci were detected by PCR-RFLP. Results The distributions of COL1A1 TT genotype , COL5A1 CC genotype and GDF-5 CC genotype were decreased in injured group compared with the control group. The COL12A1,COL14A1, TNC gene polymorphic loci showed no significant difference between two groups. The COL1A1, COL5A1 and GDF-5 genes were involved in encoding for collagen, matrix metallopeptidase, tenascin and growth factors which protect the athletic from the musculoskeletal injuries, particularly in tendon and ligament tissues. Conclusions The genetic loci will help to identify individuals with advantageous physical performance and a lower chance of suffering from injuries.

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