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Mesenchymal stem cells arthritis

Luminita Labusca, Florin Zugun-Eloae
Intra-articular adipose tissue deposits known as articular fat pads (AFPs) are described to exist within synovial joints. Their assumed role in normal joint biomechanics is increasingly objectivized by means of advanced methods of functional imaging. AFPs possess structural similarity with body subcutaneous white adipose tissue (WAT), however, seems to be regulated by independent metabolic loops. AFP dimension are conserved during extreme WAT states: obesity, metabolic syndrome, lipodystrophy, and cachexia...
2018: Frontiers in Veterinary Science
Sara Žigon-Branc, Ariana Barlič, Miomir Knežević, Matjaž Jeras, Gordana Vunjak-Novakovic
Inflammation plays a major role in progression of rheumatoid arthritis (RA), a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors...
March 14, 2018: Biotechnology Progress
Yuji Kohno, Mitsuru Mizuno, Nobutake Ozeki, Hisako Katano, Koji Otabe, Hideyuki Koga, Mikio Matsumoto, Haruka Kaneko, Yuji Takazawa, Ichiro Sekiya
BACKGROUND: Mobilization of mesenchymal stem cells (MSCs) from the synovium was revealed using a "suspended synovium culture model" of osteoarthritis (OA). The pathology of rheumatoid arthritis (RA) differs from that of OA. We investigated whether mobilization of MSCs from the synovium also occurred in RA, and we compared the properties of synovial MSCs collected from suspended synovium culture models of RA and OA. METHODS: Human synovium was harvested during total knee arthroplasty from the knee joints of patients with RA (n = 8) and OA (n = 6)...
March 9, 2018: BMC Musculoskeletal Disorders
Stella Cosenza, Karine Toupet, Marie Maumus, Patricia Luz-Crawford, Olivier Blanc-Brude, Christian Jorgensen, Danièle Noël
Objectives: Mesenchymal stem cells (MSCs) release extracellular vesicles (EVs) that display a therapeutic effect in inflammatory disease models. Although MSCs can prevent arthritis, the role of MSCs-derived EVs has never been reported in rheumatoid arthritis. This prompted us to compare the function of exosomes (Exos) and microparticles (MPs) isolated from MSCs and investigate their immunomodulatory function in arthritis. Methods: MSCs-derived Exos and MPs were isolated by differential ultracentrifugation. Immunosuppressive effects of MPs or Exos were investigated on T and B lymphocytes in vitro and in the Delayed-Type Hypersensitivity (DTH) and Collagen-Induced Arthritis (CIA) models...
2018: Theranostics
Chen Zhao, Wei Jiang, Nian Zhou, Junyi Liao, Mingming Yang, Ning Hu, Xi Liang, Wei Xu, Hong Chen, Wei Liu, Lewis L Shi, Leonardo Oliveira, Jennifer Moriatis Wolf, Sherwin Ho, Aravind Athiviraham, H M Tsai, Tong-Chuan He, Wei Huang
Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) induces effective chondrogenesis of mesenchymal stem cells (MSCs) and can thus be explored as a potential therapeutic agent for cartilage defect repair...
December 2017: Genes & Diseases
Kijun Lee, Narae Park, Hyerin Jung, Yeri Alice Rim, Yoojun Nam, Jennifer Lee, Sung-Hwan Park, Ji Hyeon Ju
Human bone marrow-derived mesenchymal stem cells (MSCs) have been observed to inhibit arthritis in experimental animal models such as collagen-induced arthritis. However, the exact anti-inflammatory mechanisms remain poorly understood. Interleukin-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine produced by immune and stromal cells. We postulated that MSCs could produce IL-1Ra and attenuate experimental arthritis. In this study, 5x106 MSCs were injected into the peritoneal cavity of IL-1Ra knockout (IL-1RaKO) mice...
2018: PloS One
Hongrui Liu, Dongfang Li, Yi Zhang, Minqi Li
Achieving satisfactory reconstruction of bone remains an important goal in orthopedic and dental conditions such as bone trauma, osteoporosis, arthritis, osteonecrosis, and periodontitis. Appropriate temporal and spatial differentiation of mesenchymal stem cells (MSCs) is essential for postnatal bone regeneration. Additionally, an acute inflammatory response is crucial at the onset of bone repair, while an adaptive immune response has important implications during late bone remodeling. Various reports have indicated bidirectional interactions between MSCs and inflammatory cells or molecules...
February 12, 2018: Histochemistry and Cell Biology
Chijian Zuo, Xiaoying Zhao, Yu Shi, Wen Wu, Ning Zhang, Jiake Xu, Chuandong Wang, Guoli Hu, Xiaoling Zhang
Although the mechanisms of Tumor necrosis factor alpha (TNF-α) on facilitating osteoclast differentiation and bone resorption is well known, the mechanisms behind the suppression of the osteoblast differentiation from mesenchymal stem cells (MSCs) are still poorly understood. In this study, we observed a negative correlation between TNF-α levels and the expression of special AT-rich sequence-binding protein 2 (SATB2), a critical osteoblastogenesis transcription factor, in ovariectomy (OVX)-induced bone loss and IL-1-induced arthritis animal model...
January 12, 2018: Oncotarget
Miguel Tofiño-Vian, Maria Isabel Guillén, Maria José Alcaraz
Extracellular vesicles (EVs) are attracting increasing interest since they might represent a more convenient therapeutic tool with respect to their cells of origin. In the last years much time and effort have been expended to determine the biological properties of EVs from mesenchymal stem cells (MSCs) and other sources. The immunoregulatory, anti-inflammatory and regenerative properties of MSC EVs have been demonstrated in in vitro studies and animal models of rheumatoid arthritis or osteoarthritis. This cell-free approach has been proposed as a possible better alternative to MSC therapy in autoimmune conditions and tissue regeneration...
February 7, 2018: Biochemical Pharmacology
Vida Nazemian, Homa Manaheji, Ali Mohammad Sharifi, Jalal Zaringhalam
Neuroinflammation plays a crucial role in expression of symptoms of numerous autoimmune and neurodegenerative diseases such as pain during rheumatoid arthritis. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways have been strongly implicated in the generation of pathological pain states, particularly at central nervous system sites and induction of spinal neuroinflammatory symptoms. The wide ranges of research to define new therapeutic approaches, including neuroimmune-modulators like stem cells are in progress...
January 31, 2018: Cellular and Molecular Biology
Yue Sun, Wei Deng, Genhong Yao, Weiwei Chen, Xiaojun Tang, Xuebing Feng, Liwei Lu, Lingyun Sun
Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2)...
January 23, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Sahar Sobhy Abd Elhalem, Nawal Zakaria Haggag, Nashwa Ahmed El-Shinnawy
Interleukin-9 (IL-9) has been shown to be upregulated in rheumatoid arthritis (RA). The exact role of IL-9 has not yet been effectively studied. Mesenchymal stem cells (MSCs) have shown a promising immunomodulatory role towards repairing cartilage and restoring joint function. One of the key problems influencing the therapeutic efficacy of stem cell therapy is the poor cell survival following transplantation. This is attributed to oxidative and inflammatory stresses at the injured sites. Hesperidin (Hsd), a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-oxidant and anti-inflammatory activities...
January 23, 2018: Autoimmunity
Zhuan Feng, Yue Zhai, Zhaohui Zheng, Lijie Yang, Xing Luo, Xiwen Dong, Qing Han, Jin Jin, Zhi-Nan Chen, Ping Zhu
Mesenchymal stem cells (MSCs) are multi-potent cells that are self-renewable and possess the potential to differentiate into multiple lineages. Several studies demonstrated that MSCs could regulate a Th17/Treg balance and could be a potential therapeutic target for Rheumatoid Arthritis (RA). A20 is highly expressed in many cell types after the stimulation of TNF-α, where it may inhibit pro-inflammatory cytokine secretion. However, the expression of A20 in BM-MSCs in RA is not fully understood. In our study, we found that A20 was decreased in RA patients' bone marrow MSCs (BM-MSCs), and with more IL-6 secretion, the balance of Th17/Treg was broken...
January 11, 2018: Scientific Reports
Toru Ichiseki, Miyako Shimazaki, Yoshimichi Ueda, Shusuke Ueda, Masanobu Tsuchiya, Daisuke Souma, Ayumi Kaneuji, Norio Kawahara
Persistent inflammation is well known to promote the progression of arthropathy. mesenchymal stem cells (MSCs) have been shown to possess anti-inflammatory properties and tissue differentiation potency. Although the experience so far with the intraarticular administration of mesenchymal stem cell (MSC) to induce cartilage regeneration has been disappointing, MSC implantation is now being attempted using various surgical techniques. Meanwhile, prevention of osteoarthritis (OA) progression and pain control remain important components of the treatment of early-stage OA...
January 9, 2018: International Journal of Molecular Sciences
Magdalena Krajewska-Włodarczyk, Agnieszka Owczarczyk-Saczonek, Waldemar Placek, Adam Osowski, Piotr Engelgardt, Joanna Wojtkiewicz
Considerable progress has been made recently in understanding the complex pathogenesis and treatment of spondyloarthropathies (SpA). Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although they adequately control inflammatory symptoms, they do not affect the abnormal bone formation processes associated with SpA. However, the traditional therapeutic approach does not cover the regenerative treatment of damaged tissues...
December 28, 2017: International Journal of Molecular Sciences
Kazuo Okamoto
  Bone is a component of the skeletal-locomotor system but also functions as an immunological organ that harbors hematopoietic stem and progenitor cells. Since the immune and skeletal systems are closely related through a number of shared regulatory molecules including cytokines and receptors, bone can be affected in various immune disorders. Rheumatoid arthritis is a typical disease in which the immune system affects the bone metabolism. The enhanced activity of osteoclasts by the activation of Th17 cells causes the joint destruction in rheumatoid arthritis...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Urszula Skalska, Ewa Kuca-Warnawin, Anna Kornatka, Iwona Janicka, Urszula Musiałowicz, Tomasz Burakowski, Ewa Kontny
Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from rheumatoid arthritis (RA) patients undergoing total knee joint replacement surgery...
December 2017: Autoimmunity
Nedime Serakinci, Gokce Savtekin
Stem cells have self-renewal capacity and an ability to differentiate into particular cell types generating mature cells. Mesenchymal stem cells (MSCs) have a significant role in tissue homeostasis, which leads into tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs are also believed to have therapeutic power over temporomandibular joint (TMJ) disorders (TMDs). The most common type of TMD is articular disc displacement, which induces progressive degenerative changes...
2017: Critical Reviews in Eukaryotic Gene Expression
Kyung-Ah Cho, Minhwa Park, Yu-Hee Kim, Kyung-Ha Ryu, So-Youn Woo
Th17 cells play a critical role in several autoimmune diseases, including psoriasis and psoriatic arthritis (PsA). Psoriasis is a chronic inflammatory skin disease associated with systemic inflammation and comorbidities, such as PsA. PsA develops in nearly 70% of patients with psoriasis, and osteoclasts associated bone erosion is a hallmark of the disease. Thus far, the effect of Th17 cells on osteoclastogenesis via direct cell-to-cell interactions is less understood. In this study, we observed that Th17 cells directly promote osteoclast differentiation and maturation via expression of receptor activator of nuclear factor-κ β ligand (RANKL) in vitro...
October 13, 2017: Oncotarget
Massimiliano Leigheb, Michela Bosetti, Antonio De Consoli, Alessia Borroni, Mario Cannas, Federico Grassi
Articular cartilage repair is still a challenge. To date evidence is insufficient to support a treatment over the others. Inflammatory conditions in the joint hamper the application of tissue engineering during chronic joint diseases. Most of the Matrix Autologous Chondrocyte Implantation (MACI) cases reported in literature do not deal with rheumatoid knees and do not have a long clinical-histologic follow-up. We report about a 46-year old woman who suffered of a painful focal Outerbridge 4th degree chondral lesion in the medial femoral condyle of her left rheumatoid knee...
October 18, 2017: Acta Bio-medica: Atenei Parmensis
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