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1.
This study investigated the combined application of Transforming Growth Factor beta-1 (TGFbeta-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate osteogenic expression in vitro. TGFbeta-1 and BMP-2 fulfill specific roles in the formation of new bone. COLLOSS E, a bone-derived collagen product containing a variety of naturally occurring growth factors, was also used. Growth factors were administered to osteoblast-like cells from rat bone marrow (RBM). Proliferation and differentiation were monitored up to 24 days, by measuring total DNA content, alkaline phosphatase activity, and calcium content. Genetic expression of a set of differentiation markers at day 7 was measured by Q-PCR. Adding BMP-2 alone induced high proliferation rates, compared to the growth factor supplemented groups, and it induced high differentiation rates, compared to the control group. Adding TGFbeta-1 combined with BMP-2, TGFbeta-1 alone, or COLLOSS E resulted in a significant decrease in proliferation rate, but an increase in differentiation rate, compared to the control group. Additive or synergistic effects of application of TGFbeta-1 and BMP-2 were not observed. The observed effects of COLLOSS E mainly resembled those of TGFbeta-1 application alone. It can be concluded that BMP-2 is the most suitable candidate for osteogenic stimulation of RBM cells in these settings.  相似文献   

2.
Tenocyte mechanotransduction has been of great interest to researchers in tendon mechanobiology and biomechanics. In vivo, tenocytes are subjected to tensile strain and fluid shear stress, but most studies of tenocyte mechanobiology have been to understand how tenocytes regulate their functions in response to tensile strain. Thus, there is still much to know about tenocyte responses to fluid shear stress, partly due to the difficulty of devising a suitable experimental set-up and understanding the exact magnitude of imposed fluid shear stress. Therefore, this study was performed to test a new experimental system, which is suitable for the application of tensile strain and fluid shear stress to tenocytes in vitro. It was experimentally and numerically confirmed that tenocytes could maintain their in situ morphology within microfabricated microgrooves; also, physiological tensile strain and a wide range of fluid shear stress magnitudes can be applied to these cells. Indeed, it was demonstrated that the combined stimulation of cyclic tensile strain and oscillatory fluid shear stress induced a greater synergetic effect on tenocyte calcium response and significantly increased the percentage of tenocyte exhibiting increases in intracellular Ca2+ concentration compared to the solo applications of these two modes of mechanical stimulation. The experimental system presented here is suitable for research of tenocyte mechanobiology, particularly mechanotransduction events, which were difficult to study using previous experimental models like explants and cell monolayers.  相似文献   

3.
Liu W  Chen B  Deng D  Xu F  Cui L  Cao Y 《Tissue engineering》2006,12(4):775-788
Harvesting autologous tenocytes for tendon engineering may cause secondary tendon defect at the donor site. Dermal fibroblasts are an easily accessible cell source and do not cause major donor site defect. This study aims to explore the possibility of tendon engineering using dermal fibroblasts. A total of 45 hybrid pigs were randomly divided into three groups: experimental group (n = 15)--repair of tendon defect with a dermal fibroblast engineered tendon; control group 1 (n = 15)--repair of defect with a tenocyte engineered tendon; and control group 2 (n = 15)-repair of defect with a scaffold alone. Both autologous dermal fibroblasts and tenocytes were seeded on polyglycolic acid (PGA) unwoven fibers to form a cell-scaffold construct and cultured in vitro for 7 days before in vivo implantation to repair a defect of flexor digital superficial tendon. Specimens were harvested at weeks 6, 14, and 26 for gross, histological, and mechanical analyses. Microscopy revealed good attachment of both dermal fibroblasts and tenocytes on PGA fibers and matrix production. In vivo results showed that fibroblast and tenocyte engineered tendons were similar to each other in their gross view, histology, and tensile strength. At 6 weeks, parallel collagen alignment was observed at both ends, but not in the middle in histology, with more cellular components than natural tendons. At weeks 14 and 26, both engineered tendons exhibited histology similar to that of natural tendon. Collagens became parallel throughout the tendon structure, and PGA fibers were completely degraded. Interestingly, dermal fibroblast and tenocyte engineered tendons did not express type III collagen at 26 weeks, which remained observable in normal pig skin and control group 2 tissue using polarized microscopy, suggesting a possible phenotype change of implanted dermal fibroblasts. Furthermore, both fibroblast and tenocyte engineered tendons shared similar tensile strength, about 75% of natural tendon strength. At 6 weeks in control group 2, neo-tissue was formed only at the peripheral area by host cells. A cord-like tissue was formed at weeks 14 and 26. However, the formed tissue was histologically disorganized and mechanically weaker than both cell-engineered tendons (p < 0.05). These results suggest that dermal fibroblasts may have the potential as seed cells for tendon engineering.  相似文献   

4.
Chen B  Wang B  Zhang WJ  Zhou G  Cao Y  Liu W 《Biomaterials》2012,33(26):6086-6097
Engineering a functional tendon with strong mechanical property remains an aim to be achieved for its eventual application. Both skeletal muscle and tendon are closely associated during their development and both can bear strong mechanical loading dynamically. This study explored the possibility of engineering stronger tendons with mouse skeletal muscle derived cells (MDCs) and with mouse tenocytes as a control. The results demonstrated that both MDCs and tenocytes shared the gene expression of growth differentiation factor-8 (GDF-8), collagens I, III, VI, scleraxis and tenomodulin, but with MyoD gene expression only in MDCs. Quantitatively, MDCs expressed higher levels of GDF-8, collagens III and VI (p < 0.05), whereas tenocytes expressed higher levels of collagen I, scleraxis and tenomodulin (p < 0.05). Interestingly, MDCs proliferated faster with more cells in S + G2/M phases than tenocytes (p < 0.05). After been seeded on polyglycolic acid (PGA) fibers, MDCs formed better quality engineered tendons with more mature collagen structure and thicker collagen fibrils as opposed to tenocyte engineered tendons. Biochemically, more collagen VI and decorin were produced in the former than in the later. Functionally, MDC engineered tendons exhibited stronger mechanical properties than tenocyte engineered tendons, including maximal load, stiffness, tensile strength and Young's modulus (p < 0.05). Furthermore, with the increase of implantation time, MDCs gradually lost their expression of myogenic molecules of MyoD and desmin and gained the expression of tenomodulin, a marker for tenocytes. Collectively, these results indicate that MDCs may serve as a desirable alternative cell source for engineering functional tendon tissue.  相似文献   

5.
BACKGROUND: Airway remodeling has an important role in the pathogenesis of bronchial asthma. Many mediators that influence the pathophysiology of bronchial asthma, especially cysteinyl leukotrienes (CysLTs) and TGF-beta1, are involved in airway remodeling. OBJECTIVE: To know whether TGF-beta1 alters fibroblast responsiveness to CysLTs, we examined the effects of leukotriene (LT) D4 on collagen production from fibroblasts and from myofibroblasts transformed by TGF-beta1. We also examined whether TGF-beta1 upregulates CysLT1 receptor (CysLT1R) expression in fibroblasts. METHODS: Concentrations of procollagen in the human fetal lung fibroblast (HFL) 1 cell supernatant were measured by using an enzyme immunoassay kit in the presence or absence of various concentrations of LTD4, TGF-beta1, CysLT1R antagonist, or some combination of these. The mRNA expression of CysLT1R and alpha-smooth muscle actin as a marker of myofibroblasts was measured by means of real-time PCR. Furthermore, protein expression of CysLT1R on fibroblasts was measured by means of flow cytometric analysis. RESULTS: TGF-beta1 stimulated collagen production from HFL-1 cells, but LTD4 alone did not. LTD4 in combination with TGF-beta1 increased collagen production compared with TGF-beta1 alone. Real-time PCR showed that stimulation with TGF-beta1 significantly upregulated CysLT1R and alpha-smooth muscle actin mRNA expression in HFL-1 cells. CONCLUSIONS: LTD4 increased collagen production by upregulating CysLT1R induced by TGF-beta1. In the TGF-beta-rich milieu, activated myofibroblasts expressing CysLT1R can respond to CysLTs and produce large amounts of extracellular matrix, thereby contributing to airway remodeling. These data suggest that treatment with leukotriene receptor antagonists might prevent airway remodeling in patients with asthma.  相似文献   

6.
聚合物表面生物修饰对肌腱细胞黏附特性的影响   总被引:3,自引:0,他引:3  
为了探讨增强肌腱细胞与聚合物材料黏附力学特性的措施 ,采用生物可降解聚合物—乳酸与羟基乙酸共聚物 85 / 15 ,制成透光的薄膜 ,在膜表面裱衬聚赖氨酸的基础上 ,表面裱衬细胞外基质 ( I型胶原蛋白、纤维粘连蛋白 ,以及相应的抗体 )和生长因子 (类胰岛素生长因子 1) ,接种转化人胚肌腱细胞后 ,利用微吸管实验技术测定转化人胚肌腱细胞与聚合物薄膜的黏附力。结果显示 :在聚合物薄膜表面裱衬纤维粘连蛋白或 I型胶原蛋白 ,可明显提高转化人胚肌腱细胞与聚合物薄膜的黏附力 ( P<0 .0 5 ) ,但若在此基础上进一步分别复合裱衬纤维粘连蛋白抗体或 I型胶原蛋白抗体 ,则引起转化人胚肌腱细胞与聚合物薄膜的黏附力明显下降 ( P<0 .0 5 ) ;肌腱细胞对聚合物薄膜的黏附力与细胞外基质蛋白 (纤维粘连蛋白或 I型胶原蛋白 )的裱衬浓度有很好的依赖性 ;I型胶原蛋白和纤维粘连蛋白介导转化人胚肌腱细胞与聚合物薄膜的特异性黏附作用 ;二者复合裱衬浓度达到一定比例时 ,可产生协同作用 ,增强黏附效果 ;这种特异性黏附作用可被相应的抗体分子所抑制 ;生长因子对转化人胚肌腱细胞有明显的促黏附作用。提示 ,材料表面生物修饰可促进转化人胚肌腱细胞与聚合物的黏附作用 ,这对构建组织工程化肌腱具有重要的指导意义  相似文献   

7.
Substance P (SP) and the neurokinin-1 receptor (NK-1R) are involved in the development of colitis and mucosal healing after colonic inflammation. We studied whether SP modulates colonic fibrosis by using a chronic model of trinitrobenzenesulfonic acid (TNBS)-induced colitis in wild-type (WT) and NK-1R-deficient (NK-1R KD) mice. We found increased mRNA expression levels of collagen, vimentin, and the fibrogenic factors transforming growth factor β1 and insulin-like growth factor 1 in the chronically inflamed colons of WT mice treated with repeated intracolonic TNBS administrations. Fibrosis in TNBS-treated mice was also evident immunohistochemically by collagen deposition in the colon. Treatment of TNBS-exposed WT mice with the NK-1R antagonist CJ-12255 reduced colonic inflammation, colonic fibrosis, fibroblast accumulation, and expression levels of the fibrogenic factors. NK-1R knockout mice chronically exposed to TNBS had similar colonic inflammation compared with WT, but reduced colonic fibrosis, fibroblast accumulation, and expression levels of fibrogenic factors. Immunohistochemical staining also showed co-localization of NK-1R with fibroblasts in inflamed colons of mice and in colonic mucosa of patients with Crohn's disease. Exposure of human colonic CCD-18Co fibroblasts to SP (10 nmol/L) increased cell migration. SP stimulated collagen synthesis in CCD-18Co fibroblasts in the presence of transforming growth factor β1 and insulin-like growth factor 1, and this effect was reduced by Akt inhibition. Thus, SP, via NK-1R, promotes intestinal fibrogenesis after chronic colitis by stimulating fibrotic responses in fibroblasts.  相似文献   

8.
Abstract

The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenoctyes.

Twenty-four male Sprague–Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.  相似文献   

9.
Augmentation of the rat parotid salivary secretion to intravenous injections of substance P (SP) occurred when SP was combined with vasoactive intestinal peptide (VIP), or stimulation of the auriculo-temporal nerve in the presence of atropine and the adrenergic blockers, dihydroergotamine and propranolol. The largest increase was obtained when SP (0.5 micrograms kg-1) was used together with subthreshold doses of VIP (84% at 0.05 micrograms kg-1 and 105% at 0.5 micrograms kg-1) and low frequency stimulation (92% at 2 Hz and 97% at 5 Hz), which did not produce any salivary secretion by itself. There was no facilitated secretion when VIP and nerve stimulation were combined. Amylase output was much larger (250-500%) when SP was combined with nerve stimulation (0.5-5 Hz) or VIP (0.005-5 micrograms kg-1) than when SP was used alone. Similar results were obtained in rats where the auriculo-temporal nerve was stimulated during the early phase (24-90 h) of Wallerian degeneration, when the nerve-induced responses were seemingly completely blocked. Our results are consistent with the hypothesis that both VIP and SP contribute to the atropine-resistant parotid secretion, and that they have a complementary role in the rat parotid exocrine function.  相似文献   

10.
Tendon injuries are common clinical problems and are difficult to treat. In particular, the tendon-to-bone insertion site, once damaged, does not regenerate its complex zonal arrangement. A potential treatment for tendon injuries is to replace injured tendons with bioengineered tendons. However, the bioengineering of tendon will require a detailed understanding of the normal development of tendon, which is currently lacking. Here, we use the mouse patellar tendon as a model to describe the spatial and temporal pattern of expression of molecular markers for tendon differentiation from late fetal life to 2 weeks after birth. We found that collagen I, fibromodulin, and tenomodulin were expressed throughout the tendon, whereas tenascin-C, biglycan, and cartilage oligomeric protein were concentrated in the insertion site during this period. We also identified signaling pathways that are activated both throughout the developing tendon, for example, transforming growth factor beta and bone morphogenetic protein, and specifically in the insertion site, for example, hedgehog pathway. Using a mouse line expressing green fluorescent protein in all tenocytes, we also found that tenocyte cell proliferation occurs at highest levels during late fetal life, and declines to very low levels by 2 weeks after birth. These data will allow both the functional analysis of specific signaling pathways in tenocyte development and their application to tissue-engineering studies in vitro.  相似文献   

11.
Fibroblasts differ in a variety of phenotypic features, including the expression of Thy-1 a glycophosphatidylinositol-linked glycoprotein. Fibroblasts in idiopathic pulmonary fibrosis (IPF) are Thy-1 negative, whereas most fibroblasts from normal lungs are Thy-1 positive. However, the functional consequences of the absence of Thy-1 are not fully understood. We analyzed the expression of Thy-1 in several primary fibroblasts lines derived from IPF, hypersensitivity pneumonitis (HP), and normal human lungs. We found that a high proportion, independently of their origin, expressed Thy-1 in vitro. We identified a primary culture of HP fibroblasts, which did not express Thy-1, and compared several functional activities between Thy-1 (-) and Thy-1 (+) fibroblasts. Thy-1 (-) fibroblasts were smaller (length: 41.3±20.8?μ versus 83.1±40 μ), showed increased proliferative capacity and enhanced PDGF-induced transmigration through collagen I (59.9% versus 42.2% over control under basal conditions, P<0.01). Likewise, Thy-1 (-) fibroblasts either spontaneously or after TGF-β stimulation demonstrated stronger contraction of collagen matrices (eg, 0.17±0.03 versus 0.6±0.05 cm2 after TGF-β stimulation at 24 h; P<0.01). Thy-1 (-) lung fibroblasts stimulated with TGF-β1 expressed MMP-9, an enzyme that is usually not produced by lung fibroblasts. TGFβ-induced MMP-9 expression was reversible upon re-expression of Thy-1 after transfection with full-length Thy-1. β-glycan, a TGF-β receptor antagonist abolished MMP-9 expression. TGF-β1-induced MMP-9 in Thy-1 (-) fibroblasts depended on the activation of ERK1/2 signaling pathway. Finally, we demonstrated that fibroblasts from IPF fibroblastic foci, which do not express Thy-1 exhibit strong staining for immunoreactive MMP-9 protein in vivo. These findings indicate that loss of Thy-1 in human lung fibroblasts induces a fibrogenic phenotype.  相似文献   

12.
13.
Ultrasound is an effective noninvasive treatment for various tendinopathies. However, how tenocytes convert ultrasound stimulation into cascades of cellular and molecular events is not well understood. The purpose of this study is to elucidate the signaling pathways of tenocytes during ultrasound stimulation.

Primary cultures of tenocytes were harvested from Achilles tendons of Sprague–Dawley rats. The viability and proliferation of tenocytes, their genes expression, and the signaling pathways after ultrasound treatment with or without specific inhibitors were evaluated and analyzed.

The results showed that ultrasound treatment (100 mW/cm2 for 20 min) significantly enhanced matrix metalloproteinase 13 (MMP-13), c-Fos, and c-Jun gene expression, increased JNK and p38, but not extracellular signal-regulated kinase-1/2 (ERK1/2), phosphorylation at 5 min, and sustained up to 60 min. JNK inhibitor and p38 inhibitor, but not ERK1/2 inhibitor, attenuated ultrasound-dependent induction of MMP-13 expression, indicating that the JNK and p38 pathways are required for ultrasound-induced MMP-13 expression in tenocytes. We also found that SB431542 (transforming growth factor-beta (TGF-β) receptor kinases inhibitor) suppressed ultrasound-induced MMP‐13 and c-Fos gene expression, and p38 phosphorylation.

This study revealed that ultrasound treatment stimulates tenocytes proliferation and regulates their matrix metabolism through the cross-talk between TGF-β and ultrasound-induced mitogen-activated protein kinases (MAPKs) signaling pathways.  相似文献   

14.
Ultrasound is an effective noninvasive treatment for various tendinopathies. However, how tenocytes convert ultrasound stimulation into cascades of cellular and molecular events is not well understood. The purpose of this study is to elucidate the signaling pathways of tenocytes during ultrasound stimulation. Primary cultures of tenocytes were harvested from Achilles tendons of Sprague-Dawley rats. The viability and proliferation of tenocytes, their genes expression, and the signaling pathways after ultrasound treatment with or without specific inhibitors were evaluated and analyzed. The results showed that ultrasound treatment (100 mW/cm(2) for 20 min) significantly enhanced matrix metalloproteinase 13 (MMP-13), c-Fos, and c-Jun gene expression, increased JNK and p38, but not extracellular signal-regulated kinase-1/2 (ERK1/2), phosphorylation at 5 min, and sustained up to 60 min. JNK inhibitor and p38 inhibitor, but not ERK1/2 inhibitor, attenuated ultrasound-dependent induction of MMP-13 expression, indicating that the JNK and p38 pathways are required for ultrasound-induced MMP-13 expression in tenocytes. We also found that SB431542 (transforming growth factor-beta (TGF-β) receptor kinases inhibitor) suppressed ultrasound-induced MMP?13 and c-Fos gene expression, and p38 phosphorylation. This study revealed that ultrasound treatment stimulates tenocytes proliferation and regulates their matrix metabolism through the cross-talk between TGF-β and ultrasound-induced mitogen-activated protein kinases (MAPKs) signaling pathways.  相似文献   

15.
Qin TW  Yang ZM  Wu ZZ  Xie HQ  Qin J  Cai SX 《Biomaterials》2005,26(33):6635-6642
We report a direct measurement of the adhesion strength of human embryonic tenocytes (HETCs) and transformed human embryonic tenocytes (THETCs) to fibronectin (FN)- and type I collagen (CNI)- modified poly(DL-lactide-co-glycolide) (PLGA) substrates with a micropipette aspiration technique. PLGA substrates were first coated with poly-D-lysine (PDL), and then with various concentrations (1 microg/ml, 2 microg/ml, 5 microg/ml, and 10 microg/ml) of FN and CNI in serum-free F12 media. Anti-FN and Anti-CNI antibodies were used to inhibit attachment of tenocytes to FN- and CNI- modified substrates in a dilution range of 1:5000-1:500 and 1:1500-1:250, respectively. The substrates were employed for incubation of HETCs and THETCs for 30 min at 37 degrees C before the adhesion strength measurements. We found that the adhesion strengths showed a strong dependence on the seeding time and FN or CNI concentrations. Anti-FN and Anti-CNI antibodies significantly compromised adhesion of HETCs and THETCs to the corresponding modified substrates (P < 0.05). These findings show that FN- or CNI-modified polymer substrates offer significant advantages for tissue engineering tendon scaffolds concerning tenocyte adhesion. In addition, HETCs and THETCs bear similar biological behaviors in terms of adhesion, indicating the possibility of using THETCs in place of HETCs in tissue engineering construction of human tendons.  相似文献   

16.

Introduction

CCN4, also termed WNT-inducible signaling pathway protein-1 (WISP-1), has important roles in inflammation and tissue injury. This study aimed to investigate the effect of CCN4 inhibition using monoclonal anti-CCN4 antibody (CCN4mAb) on the liver injury and fibrosis in a mouse model of liver fibrosis.

Material and methods

The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received vehicle (saline/olive oil) by subcutaneous injection, CCl4 by subcutaneous injection or CCl4 (subcutaneous) plus CCN4mAb by subcutaneous injection. The pro-inflammatory and pro-fibrotic factors were determined by Western blot. The biochemistry and histopathology, collagen deposition and nuclear factor (NF)-κB activity were also assessed.

Results

Chronic CCl4 treatment caused liver injury and collagen accumulation. The expression levels of CCN4, pro-inflammatory and pro-fibrotic mediators as well as the activity of NF-κB were markedly increased. Treatment with CCN4mAb significantly inhibited CCl4-induced CCN4 expression, leading to attenuated CCl4-induced liver injury and the inflammatory response. CCN4 blockade also significantly reduced the formation of collagen in the liver and the expression of α-smooth muscle actin and transforming growth factor β1.

Conclusions

CCN4 inhibition by CCN4mAb in vivo significantly attenuated the CCl4-induced liver injury and the progression of liver fibrosis. CCN4 may represent a novel therapeutic target for liver injury and fibrosis.  相似文献   

17.
利用光刻技术制作微格式模板,微接触转印法制作微沟槽PDMS表面,微流道技术裱衬不同浓度的Ⅰ型胶原于微沟槽表面上,比较其对细胞生长形态及生长取向的影响.对照组为未裱衬胶原的微沟槽、平板PDMS及裱衬胶原的平板PDMS.种植SD大鼠肌腱细胞在材料上,于37℃孵箱中培养48 h.采用MTT比色法测定不同浓度的胶原对肌腱细胞的生长增殖的影响.通过倒置相差显微镜、扫描电镜、荧光显微镜观察细胞生长的形态,取向情况.结果显示:Ⅰ型胶原修饰的PDMS微沟槽材料比未裱衬胶原的对照组具有明显的促细胞生长的作用(P<0.05),并且随着胶原浓度的增加作用越明显.有微沟槽表面的材料对细胞的生长形态和生长取向有明显影响.提示,Ⅰ型胶原修饰的微沟槽材料不仅能规范肌腱细胞的生长取向,而且能促进肌腱细胞的生长,从而得到理想的细胞生长形态,该结果对工程化肌腱的构建有重要的指导意义.  相似文献   

18.
19.
Tendon injuries in humans as well as in animals' veterinary medicine are problematic because tendon has poor regenerative capacity and complete regeneration of the ruptured tendon is never achieved. In the last decade there has been an increasing need of treatment methods with different approaches. The aim of the current study was to improve the regeneration process of rat Achilles tendon with tenocyte seeded decellularized tendon matrices. For this purpose, Achilles tendons were harvested, decellularized and seeded as a mixture of three consecutive passages of tenocytes at a density of 1 × 106 cells/ml. Specifically, cells with different passage numbers were compared with respect to growth characteristics, cellular senescence and collagen/tenocyte marker production before seeding process. The viability of reseeded tendon constructs was followed postoperatively up to 6 months in rat Achilles tendon by histopathological and biomechanical analysis. Our results suggests that tenocyte seeded decellularized tendon matrix can significantly improve the histological and biomechanical properties of tendon repair tissue without causing adverse immune reactions. To the best of our knowledge, this is the first long-term study in the literature which was accomplished to prove the use of decellularized matrix in a clinically relevant model of rat Achilles tendon and the method suggested herein might have important implications for translation into the clinic.  相似文献   

20.
Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-α) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (TNFR1). The complete absence of information concerning the TNF-α system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent. Purpose: To examine expression patterns of TNF-α and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-α in tendinosis tissue. Methods: TNF-α and TNFR1 mRNA were detected via in situ hybridization. TNF-α, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-α. Results: TNF-α and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-α, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-α was measurable in tendinosis tissue. Inflammatory cells were not seen. Conclusion: This is the first evidence of the existence of the TNF-α system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-α system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-α, TNFR1, and TNFR2 suggests that the TNF-α system may be involved in tenocyte activation in Achilles tendinosis.  相似文献   

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