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Mesenchymal stem cells arthritis

Vasilina A Sergeeva, Svetlana V Kostyuk, Elizaveta S Ershova, Elena M Malinovskaya, Tatiana D Smirnova, Larisa V Kameneva, Natalia N Veiko
It has been established that cell-free DNA circulating in the bloodstream affects cells. The characteristics of cfDNA depend on the physiological state of the organism. As we showed previously, diseases can cause either GC-enrichment of the cell-free DNA pool or its oxidation. Thus, in cases of cerebral atherosclerosis, heart attack and rheumatic arthritis the cell-free DNA pool is GC-enriched and, in the case of cancer, both GC-enriched and oxidized. Herein we investigated the time-dependent effect of oxidized and GC-rich cell-free DNA on NF-kB and NRF2 signaling pathways in human mesenchymal stem cells and showed that they affect cells in different ways...
2016: Advances in Experimental Medicine and Biology
Jingqi Zeng, Fan Wang, Minzhi Mao
The present study aimed to investigate the effect of co‑culture of fibroblast‑like synoviocytes (FLS) with human umbilical cord‑mesenchymal stem cells (UC‑MSCs) on rheumatoid arthritis (RA) and to understand the mechanisms that mediate the induced changes. FLS and UC‑MSCs were isolated and cultured individually, FLS were then cultured with or without UC‑MSCs. The phenotype of UC‑MSCs was analyzed prior to co‑culture. The UC‑MSCs were successfully isolated and expanded, and exhibited a fibroblast‑like morphology...
October 2016: Molecular Medicine Reports
Jie Tian, Ke Rui, Xinyi Tang, Wenxin Wang, Jie Ma, Xinyu Tian, Yungang Wang, Huaxi Xu, Liwei Lu, Shengjun Wang
Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a population of cells which has been recognized as a new resident stem cell type in the olfactory lamina propria. OE-MSCs have been shown to exert their immunosuppressive capacity by modulating T cell responses, including up-regulation of regulatory T cells (Tregs) and down-regulation of Th1/Th17 cells. As an inflammatory cytokine, IL-17 plays a critical role in orchestrating the inflammatory response during the development of collagen-induced arthritis (CIA)...
June 23, 2016: Oncotarget
Xin Yan, Yurong Cen, Qin Wang
Previous studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-κB signaling and decreased microRNA-548e (miR-548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor β receptor signaling...
2016: Scientific Reports
E Carlos Rodriguez-Merchan
Intraarticular (IA) injections of mesenchymal stem cells (MSCs) in idiopathic osteoarthritis (OA) have shown encouraging results in the literature. Hemophilic arthropathy (HA) represents an enormous societal burden. The similarity between OA and HA is very limited. HA resembles much more to the rheumatoid arthritis because a presence of thick synovial membrane and large lymphocytes infiltration. However, in its final stages, HA resembles OA and that is when IA injections of MSCs are commonly used. In this article, we review the concept of IA injections of MSCs as a treatment for HA, using the literature on OA as an example...
August 2016: Expert Review of Hematology
Hengwei Zhang, Wen Sun, Xing Li, Mengmeng Wang, Brendan F Boyce, Matthew J Hilton, Lianping Xing
Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation in TNF transgenic (TNF-Tg) mice, a mouse model of chronic inflammatory arthritis. In the current study, we used Hes1-GFP and Hes1-GFP/TNF-Tg mice to study the distribution and dynamic change of Notch active cells in normal and inflammatory bone loss and mechanisms mediating their enhanced proliferation...
September 2016: Bone
Jose M Álvaro-Gracia, Juan A Jover, Rosario García-Vicuña, Luis Carreño, Alberto Alonso, Sara Marsal, Francisco Blanco, Victor M Martínez-Taboada, Peter Taylor, Cristina Martín-Martín, Olga DelaRosa, Ignacio Tagarro, Federico Díaz-González
OBJECTIVES: To evaluate the safety and tolerability of the intravenous administration of Cx611, a preparation of allogeneic expanded adipose-derived stem cells (eASCs), in patients with refractory rheumatoid arthritis (RA), as well as to obtain preliminary clinical efficacy data in this population. METHODS: It is a multicentre, dose escalation, randomised, single-blind (double-blind for efficacy), placebo-controlled, phase Ib/IIa clinical trial. Patients with active refractory RA (failure to at least two biologicals) were randomised to receive three intravenous infusions of Cx611: 1 million/kg (cohort A), 2 million/kg (cohort B), 4 million/kg (cohort C) or placebo, on days 1, 8 and 15, and they were followed for therapy assessment for 24 weeks...
June 7, 2016: Annals of the Rheumatic Diseases
Tzu-Hua Lin, Jukka Pajarinen, Taishi Sato, Florence Loi, Changchun Fan, Luis A Córdova, Akira Nabeshima, Emmanuel Gibon, Ruth Zhang, Zhenyu Yao, Stuart B Goodman
UNLABELLED: Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model...
September 1, 2016: Acta Biomaterialia
Alan Tyndall, Jacob M van Laar
Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution...
June 2016: La Presse Médicale
Jung-Yeon Lim, Keon-Il Im, Eun-Sol Lee, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Mesenchymal stem cells (MSCs) possess immunomodulatory properties and have potential, however, there have been conflicting reports regarding their effects in rheumatoid arthritis (RA), which causes inflammation and destruction of the joints. Through a comparative analysis of regulatory T (Treg) and IL-10-producing type 1 regulatory T (Tr1) cells, we hypothesized that Tr1 cells enhance the immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy may exert synergistic immunomodulatory effects in an experimental animal model of rheumatoid arthritis (RA)...
2016: Scientific Reports
Bo Wei, Xizhuang Bai, Kang Chen, Xiaonan Zhang
Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic disorders associated with inflammation of joints characterized by damage to the underlying cartilage and bone. Bone marrow mesenchymal stem cells (BMSCs) are candidates for regeneration of bone and cartilage, which is inhibited by inflammatory cytokines in OA and RA, in particular tumor necrosis factor-α (TNF-α). This study aimed to investigate if the c-Jun N-terminal kinases (JNK)-specific inhibitor SP600125 could enhance the anti-apoptosis and migration of BMSCs treated with TNF-α...
July 8, 2016: Biochemical and Biophysical Research Communications
Yves-Marie Pers, Lars Rackwitz, Rosanna Ferreira, Oliver Pullig, Christophe Delfour, Frank Barry, Luc Sensebe, Louis Casteilla, Sandrine Fleury, Philippe Bourin, Danièle Noël, François Canovas, Catherine Cyteval, Gina Lisignoli, Joachim Schrauth, Daniel Haddad, Sophie Domergue, Ulrich Noeth, Christian Jorgensen
UNLABELLED: : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries...
July 2016: Stem Cells Translational Medicine
Supinder Kour, Manasa G Garimella, Divya A Shiroor, Suhas T Mhaske, Snehal R Joshi, Kanupriya Singh, Subhashis Pal, Monika Mittal, Hari B Krishnan, Naibedya Chattopadhyay, Anil H Ulemale, Mohan R Wani
Osteoarthritis (OA) is a chronic disease of articular joints that leads to degeneration of both cartilage and subchondral bone. These degenerative changes are further aggravated by proinflammatory cytokines including IL-1β and TNF-α. Previously, we have reported that IL-3, a cytokine secreted by activated T cells, protects cartilage and bone damage in murine models of inflammatory and rheumatoid arthritis. However, how IL-3 protects cartilage degeneration is not yet known. In this study, we investigated the role of IL-3 on cartilage degeneration under both in vitro and in vivo conditions...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
L de Girolamo, E Kon, G Filardo, A G Marmotti, F Soler, G M Peretti, F Vannini, H Madry, S Chubinskaya
The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world's population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention...
June 2016: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
Kunihiro Yamaoka
Mesenchymal stem cell(MSC)exists throughout the body. The discovery of the immunosuppressive effect with low immunogenicity has led MSC as a new tool for cell therapy in various diseases. Within the arthritis animal model, periarticular implantation of bone marrow derived MSC with a scaffold has demonstrated treatment effect with low cell number whereas systemic administration had limited effect. Bone marrow derived MSC suppressed in vitro osteoclastogenesis and osteoblastogenesis of MSC was enhanced in the presence of IL-1β...
May 2016: Clinical Calcium
Kim Hynes, Richard Bright, Susanna Proudman, David Haynes, Stan Gronthos, Mark Bartold
BACKGROUND: Despite recent advances in the treatment of arthritis with the development of disease-modifying antirheumatic drugs, 30% of patients still fail to respond to treatment. Given the potent anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) and their ability to repair damaged cartilage, bone, and tendons, it has been proposed that MSC could be ideal for cell-based treatment of arthritis. OBJECTIVE: This systematic review investigates evidence from studies on the therapeutic efficacy of MSC in rodent models of arthritis...
August 2016: Seminars in Arthritis and Rheumatism
J Zhou, Y Wang, W Cui, J W Xie, J P Li, J Y Yang, H S Xu, L Q Liang, X Y Yang, F Lian
OBJECTIVE: To explore the therapeutic potential of transplantation of adipose derived mesenchymal stem cells (ADMSCs) in rats osteoarthritis caused by anterior cruciate ligament transection. METHODS: Rats peritoneal adipose tissues were used to extract ADMSCs.Cell morphological appearance was documented and flow cytometric cell cycle was used to identify ADMSCs. Anterior cruciate ligament transection was used to induce knee osteoarthritis in rats. ADMSCs were injected into the knee cavities...
April 5, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Koshiro Sonomoto, Kunihiro Yamaoka, Hiroaki Kaneko, Kaoru Yamagata, Kei Sakata, Xiangmei Zhang, Masahiro Kondo, Yukichi Zenke, Ken Sabanai, Shingo Nakayamada, Akinori Sakai, Yoshiya Tanaka
INTRODUCTION: Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints. METHODS: MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro...
2016: PloS One
Elena Gonzalo-Gil, María J Pérez-Lorenzo, María Galindo, Rafael Díaz de la Guardia, Belén López-Millán, Clara Bueno, Pablo Menéndez, José L Pablos, Gabriel Criado
BACKGROUND: The immunosuppressive and anti-inflammatory properties of mesenchymal stromal cells (MSC) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis. Adult MSC are finite and their clinical use is restricted by the need for long-term expansion protocols that can lead to genomic instability. Inhibition of Smad2/3 signaling in human pluripotent stem cells (hPSC) provides an infinite source of MSC that match the phenotype and functional properties of adult MSC...
2015: Arthritis Research & Therapy
Gali Shalev-Malul, David C Soler, Anthony E Ting, Nicholas A Lehman, Emma Barnboym, Thomas S McCormick, Donald D Anthony, Hillard M Lazarus, Arnold I Caplan, Maya Breitman, Nora G Singer
UNLABELLED: Cell-based therapy has potential therapeutic value in autoimmune diseases such as rheumatoid arthritis (RA). In RA, reduction of disease activity has been associated with improvement in the function of regulatory T cells (Treg) and attenuated responses of proinflammatory effector T cells (Teff). Mesenchymal stem cells (MSCs) and related multipotent adult progenitor cells (MAPC) have strong anti-inflammatory and immunomodulatory properties and may be able to "reset" the immune system to a pre-RA state...
May 2016: Stem Cells Translational Medicine
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