scholarly journals CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

2021 ◽  
Vol 22 (18) ◽  
pp. 9729
Author(s):  
Neil Marr ◽  
Richard Meeson ◽  
Elizabeth F. Kelly ◽  
Yongxiang Fang ◽  
Mandy J. Peffers ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Focal Lesion ◽  
Post Injury ◽  
Surface Receptors ◽  
Basement Membrane Protein ◽  
Injury Model ◽  
Cell Niche

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

scholarly journals Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

2021 ◽  
Vol 22 (11) ◽  
pp. 5619
Author(s):  
Iris Ribitsch ◽  
Andrea Bileck ◽  
Alexander D. Aldoshin ◽  
Maciej M. Kańduła ◽  
Rupert L. Mayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Inflammatory Factors ◽  
Large Animal ◽  
Post Injury ◽  
Tendon Regeneration ◽  
Large Animal Models

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

Effect of rhPDGF-BB-Coated Sutures on Tendon Healing in a Rat Model: A Histological and Biomechanical Study

2011 ◽  
Author(s):  
S. Cummings ◽  
J. Dines ◽  
C. K. Hee ◽  
H. K. Kestler ◽  
C. M. Roden ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Biomechanical Study ◽  
Growth Factor Delivery ◽  
Delivery Method

Delivering growth factors to the site of injury using a coated suture delivery method has been investigated recently as a means to augment tissue repair [1]. This is a practical approach for growth factor delivery, as sutures are the method of choice for most orthopaedic surgeons for soft tissue repairs. One advantage of growth factor-coated sutures in tendon repair is the potential to accelerate healing in vivo, thereby improving the outcome of the repair. In particular, platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including tenocytes, and has been shown to improve healing when applied to animal models of tendon injury [2,3]. The aim of this study was to compare the quality of the tendon repair at four weeks post treatment with sutures coated with varying concentrations of rhPDGF-BB, relative to buffer-coated suture repairs.

Pifithrin-α, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

2007 ◽  
Vol 292 (1) ◽  
pp. R321-R327 ◽  
Author(s):  
David Marsolais ◽  
Claude H. Côté ◽  
Jérôme Frenette
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Process ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Acute Injury ◽  
Inflammatory Phase ◽  
Load To Failure ◽  
Transcription Factor P53

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-α, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-α during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-α failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-α increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-α reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-α on load to failure and stiffness was also evaluated. The administration of pifithrin-α during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin-α group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-α alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

scholarly journals Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yonghui Hou ◽  
Bingyu Zhou ◽  
Ming Ni ◽  
Min Wang ◽  
Lingli Ding ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Biomechanical Testing ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Rna Seq ◽  
Injury Model ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
And Control

Abstract Background Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.

scholarly journals Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study

PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0229914 ◽  
Author(s):  
Clarissa Gissi ◽  
Annalisa Radeghieri ◽  
Cristina Antonetti Lamorgese Passeri ◽  
Marialucia Gallorini ◽  
Lucia Calciano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Pilot Study ◽  
Tendon Repair ◽  
Tendon Injury ◽  
Dependent Manner ◽  
Injury Model ◽  
Dose Dependent ◽  
Stromal Stem Cells ◽  
Rat Bone

Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model

2017 ◽  
Vol 45 (6) ◽  
pp. 1429-1439 ◽  
Author(s):  
Sang Yoon Lee ◽  
Bomi Kwon ◽  
Kyoungbun Lee ◽  
Young Hoon Son ◽  
Sun G. Chung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tendon Healing ◽  
Collagen Type I ◽  
Tendon Injury ◽  
Cell Group ◽  
Type I ◽  
Injury Model ◽  
Human Specific

Background: Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model. Study Design: Controlled laboratory study. Methods: The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (106 cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling. Results: hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups. Conclusion: Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute their own proteins to tendon healing. Clinical Relevance: In tendon injury, MSCs can enhance tendon healing by secreting their own protein and have potential as a therapeutic option in human tendinopathy.

The effect of tendon stem/progenitor cell (TSC) sheet on the early tendon healing in a rat Achilles tendon injury model

2016 ◽  
Vol 42 ◽  
pp. 136-146 ◽  
Author(s):  
Issei Komatsu ◽  
James H-C. Wang ◽  
Kiyotaka Iwasaki ◽  
Tatsuya Shimizu ◽  
Teruo Okano
Keyword(s):  
Achilles Tendon ◽  
Progenitor Cell ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Injury Model

scholarly journals Platelet HMGB1 in Platelet-Rich Plasma Promotes Tendon Wound Healing

2021 ◽  
Author(s):  
Jianying Zhang ◽  
Feng Li ◽  
Tyler Augi ◽  
Kelly M. Williamson ◽  
Kentaro Onishi ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Tendon Healing ◽  
High Mobility ◽  
Tendon Injury ◽  
Tendon Injuries ◽  
Stem Cell Markers ◽  
Wound Area ◽  
Injury Model ◽  
Collagen Iii ◽  
Cell Densities

AbstractPlatelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics, but clinical trials often produce conflicting results. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a chemoattractant that can recruit stem cells to the wound area to enhance healing; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP to enhance healing in an acute patellar tendon injury model in PLT HMGB1 knockout (KO) mice and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1 KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1 KO mice showed better healing with PRP from HMGB1 KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1 KO mice. Thus, PLT HMGB1 within PRP plays an important role in the healing of wounded tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may be affected by PLT HMGB1 within PRP preparations.

scholarly journals Basic Research on Tendon Repair: Strategies, Evaluation, and Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhi Jie Li ◽  
Qian Qian Yang ◽  
You Lang Zhou
Keyword(s):  
Wound Healing ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Tendon Repair ◽  
Continuous Optimization ◽  
Tendon Healing ◽  
Basic Research ◽  
Clinical Problem ◽  
Tendon Injury ◽  
Wound Healing Process

Tendon is a fibro-elastic structure that links muscle and bone. Tendon injury can be divided into two types, chronic and acute. Each type of injury or degeneration can cause substantial pain and the loss of tendon function. The natural healing process of tendon injury is complex. According to the anatomical position of tendon tissue, the clinical results are different. The wound healing process includes three overlapping stages: wound healing, proliferation and tissue remodeling. Besides, the healing tendon also faces a high re-tear rate. Faced with the above difficulties, management of tendon injuries remains a clinical problem and needs to be solved urgently. In recent years, there are many new directions and advances in tendon healing. This review introduces tendon injury and sums up the development of tendon healing in recent years, including gene therapy, stem cell therapy, Platelet-rich plasma (PRP) therapy, growth factor and drug therapy and tissue engineering. Although most of these therapies have not yet developed to mature clinical application stage, with the repeated verification by researchers and continuous optimization of curative effect, that day will not be too far away.

Evaluation of a Novel Degradable Synthetic Biomaterial Patch for Augmentation of Tendon Healing in a Large Animal Model

2018 ◽  
Vol 32 (05) ◽  
pp. 434-440 ◽  
Author(s):  
Wayne Gersoff ◽  
Chantelle Bozynski ◽  
Cristi Cook ◽  
Ferris Pfeiffer ◽  
Keiichi Kuroki ◽  
...  
Keyword(s):  
Biomechanical Testing ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Standard Of Care ◽  
Tendon Injury ◽  
Large Animal Model ◽  
Large Animal ◽  
Range Of Movement ◽  
Limb Function ◽  
Group Outcomes

AbstractTendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.

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