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Stem cells and tendinopathy

Ying-Fei Lu, Yang Liu, Wei-Ming Fu, Jia Xu, Bin Wang, Yu-Xin Sun, Tian-Yi Wu, Liang-Liang Xu, Kai-Ming Chan, Jin-Fang Zhang, Gang Li
Tendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration...
November 28, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Shao-Yong Xu, Shu-Fen Li, Guo-Xin Ni
BACKGROUND Although tendinopathy is common, its underlying pathogenesis is poorly understood. This study aimed to investigate the possible pathogenesis of tendinopathy. MATERIAL AND METHODS In this study, a total of 24 rats were randomly and evenly divided into a control (CON) group and a strenuous treadmill running (STR) group. Animals in the STR group were subjected to a 12-week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological observation or biochemical analyses...
October 15, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Daniel J Leong, Hui B Sun
Tendon injuries are common and present a clinical challenge because they often respond poorly to treatment and require prolonged rehabilitation. Current treatments often do not completely repair or regenerate the injured or diseased tendon to its native composition, structure, and mechanical properties. Stem cell-based therapies have brought new hope for tissue repair and regeneration, including that for tendon rupture and tendinopathy. Despite tremendous effort and progress, the success of stem cell-based studies on tendon repair and regeneration has mainly been limited to preclinical studies with few clinical applications...
November 2016: Annals of the New York Academy of Sciences
James H-C Wang, Xavier Nirmala
Tendon injuries like tendinopathy are a serious healthcare problem in the United States. However, current treatments for tendon injuries are largely palliative. Biologics treatments, including tendon stem/progenitor cells (TSCs) and platelet rich plasma (PRP) hold great potential to effectively treat tendon injuries. TSCs are tendon specific stem cells and have the ability to differentiate into tenocytes, the resident tendon cells responsible for tendon homeostasis and tendon repair in case of an injury. TSCs can also self-renew and thus can replenish the tendon with tendon cells (TSCs and tenocytes) to maintain a healthy tendon...
June 2016: Operative Techniques in Orthopaedics
Helen L Birch, Mandy J Peffers, Peter D Clegg
Tendon functional competence and structural integrity rely on homeostasis of tendon cell metabolism and extracellular matrix macromolecules. The clear link between tendinopathies and increasing age suggests a slow change to tendon homeostasis, which increases susceptibility to damage. Despite this well evidenced association between increasing age and tendon damage, changes to tendon mechanical properties with ageing are not clear with different studies reporting conflicting results. More recent research suggests that age-related changes occur at specific sub-structure locations and may be overlooked by measuring properties of the whole tendon...
2016: Advances in Experimental Medicine and Biology
James H-C Wang, Issei Komatsu
Millions of people suffer from tendon injuries in both occupational and athletic settings. However, the restoration of normal structure and function to injured tendons still remains as one of the greatest challenges in orthopaedics and sports medicine. In recent years, a remarkable advancement in tendon research field has been the discovery of tendon stem/progenitor cells (TSCs). Unlike tenocytes, the predominant resident cell in tendons, TSCs have the ability to self-renew and multi-differentiate. Because of these distinct properties, TSCs may play a critical role in tendon physiology as well as pathology such as tendinopathy, which is a prevalent chronic tendon injury...
2016: Advances in Experimental Medicine and Biology
D J Griffon, J Cho, J R Wagner, C Charavaryamath, J Wei, A Wagoner Johnson
Chitosan opens new perspectives in regenerative medicine as it enhances the properties of mesenchymal stem cells (MSCs) through formation of spheroids. Hypoxia has also been proposed to enhance stemness and survival of MSCs after in vivo implantation. These characteristics are relevant to the development of an off-the-shelf source of allogenic cells for regenerative therapy of tendinopathies. Umbilical cord-derived MSCs (UCM-MSCs) offer an abundant source of immature and immunoprivileged stem cells. In this study, equine UCM-MSCs (eqUCM-MSCs) conditioned for 3 and 7 days on chitosan films at 5% oxygen were compared to eqUCM-MSCs under standard conditions...
2016: Stem Cells International
Michaela Kopka, James P Bradley
Biologic agents are gaining popularity in the management of bony and soft tissue conditions about the knee. They are becoming the mainstay of nonoperative therapy in the high-demand athletic population. The most well-studied agents include platelet-rich plasma (PRP) and stem cells-both of which have shown promise in the treatment of various conditions. Animal and clinical studies have demonstrated improved outcomes following PRP treatment in early osteoarthritis of the knee, as well as in chronic patellar tendinopathy...
July 2016: Journal of Knee Surgery
Xin Zhang, Yu-Cheng Lin, Yun-Feng Rui, Hong-Liang Xu, Hui Chen, Chen Wang, Gao-Jun Teng
Tendinopathy is a tendon disorder characterized by activity-related pain, local edema, focal tenderness to palpation, and decreased strength in the affected area. Tendinopathy is prevalent in both athletes and the general population, highlighting the need to elucidate the pathogenesis of this disorder. Current treatments of tendinopathy are both conservative and symptomatic. The discovery of tendon stem/progenitor cells (TSPCs) and erroneous differentiation of TSPCs have provided new insights into the pathogenesis of tendinopathy...
2016: Stem Cells International
Lei Zhang, Shuo Chen, Peng Chang, Nirong Bao, Chao Yang, Yufan Ti, Liwu Zhou, Jianning Zhao
BACKGROUND: Platelet-rich plasma (PRP) is now widely used as a promising treatment for patients with tendinopathy. However, the efficacy of PRP treatment for tendinopathy is controversial mainly because of inconsistent results from human clinical trials and particularly because the concentration and effect of leukocytes in PRP remain largely unknown. HYPOTHESIS: Leukocyte-rich PRP (L-PRP) inhibits growth factor release, decreases proliferation, and induces nontenocyte differentiation of tendon stem cells (TSCs); increases catabolic cytokine concentrations; and causes inflammation and apoptosis...
August 2016: American Journal of Sports Medicine
Robert F LaPrade, Andrew G Geeslin, Iain R Murray, Volker Musahl, Jason P Zlotnicki, Frank Petrigliano, Barton J Mann
Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries...
December 2016: American Journal of Sports Medicine
Takashi Oshita, Morikuni Tobita, Satoshi Tajima, Hiroshi Mizuno
BACKGROUND: Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model...
August 2016: American Journal of Sports Medicine
Jinjuan Yang, Qianjun Zhao, Kunfu Wang, Hao Liu, Caiyun Ma, Hongmei Huang, Yingjie Liu
The lack of appropriate candidates of cell sources for cell transplantation has hampered efforts to develop therapies for tendon injuries, such as tendon rupture, tendonitis, and tendinopathy. Tendon-derived stem cells (TDSCs) are a type of stem cells which may be used in the treatment of tendon injuries. In this study, TDSCs were isolated from 5-mo-old Luxi Yellow fetal bovine and cultured in vitro and further analyzed for their biological characteristics using immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR) assays...
September 2016: In Vitro Cellular & Developmental Biology. Animal
Daniel W Youngstrom, Jade E LaDow, Jennifer G Barrett
Tendons are frequently damaged and fail to regenerate, leading to pain, loss of function, and reduced quality of life. Mesenchymal stem cells (MSCs) possess clinically useful tissue-regenerative properties and have been exploited for use in tendon tissue engineering and cell therapy. However, MSCs exhibit phenotypic heterogeneity based on the donor tissue used, and the efficacy of cell-based treatment modalities may be improved by optimizing cell source based on relative differentiation capacity. Equine MSCs were isolated from bone marrow (BM), adipose (AD), and tendon (TN), expanded in monolayer prior to seeding on decellularized tendon scaffolds (DTS), and cell-laden constructs were placed in a bioreactor designed to mimic the biophysical environment of the tendon...
March 30, 2016: Connective Tissue Research
Jia-Jie Hu, Zi Yin, Wei-Liang Shen, Yu-Bin Xie, Ting Zhu, Ping Lu, You-Zhi Cai, Min-Jian Kong, Boon Chin Heng, Yi-Ting Zhou, Wei-Shan Chen, Xiao Chen, Hong-Wei Ouyang
Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves...
April 2016: Stem Cells
Ting Yuan, Jianying Zhang, Guangyi Zhao, Yiqin Zhou, Chang-Qing Zhang, James H-C Wang
Previous animal studies have shown that long term rat treadmill running induces over-use tendinopathy, which manifests as proteoglycan accumulation and chondrocytes-like cells within the affected tendons. Creating this animal model of tendinopathy by long term treadmill running is however time-consuming, costly and may vary among animals. In this study, we used a new approach to develop an animal model of tendinopathy using kartogenin (KGN), a bio-compound that can stimulate endogenous stem/progenitor cells to differentiate into chondrocytes...
2016: PloS One
Laura Leone, Salvatore Raffa, Mario Vetrano, Danilo Ranieri, Florence Malisan, Cristina Scrofani, Maria Chiara Vulpiani, Andrea Ferretti, Maria Rosaria Torrisi, Vincenzo Visco
Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors...
February 9, 2016: Oncotarget
Jayesh Dudhia, Patricia Becerra, Miguel A Valdés, Francisco Neves, Neil G Hartman, Roger K W Smith
Recent advances in the application of bone marrow mesenchymal stem cells (BMMSC) for the treatment of tendon and ligament injuries in the horse suggest improved outcome measures in both experimental and clinical studies. Although the BMMSC are implanted into the tendon lesion in large numbers (usually 10 - 20 million cells), only a relatively small number survive (<10%) although these can persist for up to 5 months after implantation. This appears to be a common observation in other species where BMMSC have been implanted into other tissues and it is important to understand when this loss occurs, how many survive the initial implantation process and whether the cells are cleared into other organs...
December 9, 2015: Journal of Visualized Experiments: JoVE
Aurélie Vandenberghe, Sarah Y Broeckx, Charlotte Beerts, Bert Seys, Marieke Zimmerman, Ineke Verweire, Marc Suls, Jan H Spaas
Suspensory ligament injuries are a common injury in sport horses, especially in competing dressage horses. Because of the poor healing of chronic recalcitrant tendon injuries, this represents a major problem in the rehabilitation of sport horses and often compromises the return to the initial performance level. Stem cells are considered as a novel treatment for different pathologies in horses and humans. Autologous mesenchymal stem cells (MSCs) are well known for their use in the treatment of tendinopathies; however, recent studies report a safe use of allogeneic MSCs for different orthopedic applications in horses...
2015: Frontiers in Veterinary Science
Bo Chen, Kanglai Tang, Jiqiang Zhang, Yupeng Guo, Xiangzhou Liu, Youxin Shi
OBJECTIVE: To investigate the effect of cytoskeleton modification on the adipogenic differentiation of rat Achilles-derived tendon stem cells (TSCs) in vitro. METHODS: TSCs were isolated from the tendon tissue of male Sprague Dawley rats (aged 3 weeks) by enzymatic digestion method and cultured for 3 passages. After the 3rd passage cells were cultured with DMEM medium containing 15% fetal bovine serum and cytochalasin D (CYD) at the concentrations of 0, 50, 100, 500, and 1 000 ng/mL, the cell survival condition and morphology changes were observed by inverted phase contrast microscope, the cytoskeleton was observed through fibrous actin (F-actin) staining, and the ratio of F-actin/ soluble globular actin (G-actin) was detected and calculated through Western blot...
February 2015: Chinese Journal of Reparative and Reconstructive Surgery
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