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Fabiana da Silva Lima, Amanda Batista da Rocha Romero, Araceli Hastreiter, Amanda Nogueira-Pedro, Edson Makiyama, Célia Colli, Ricardo Ambrósio Fock
Magnesium (Mg2+ ) is a mineral with the ability to influence cell proliferation and to modulate inflammatory/immune responses, due to its anti-inflammatory properties. In addition, mesenchymal stem cells (MSCs) modulate the function of all major immune cell populations. Knowing that, the current work aimed to investigate the effects of Mg2+ enrichment, and its influence on the immunomodulatory capacity of MSCs. Murine C3H/10T1/2 MSCs were cultivated in media with different concentrations of Mg2+ (0, 1, 3 and 5 mM), in order to evaluate the effects of Mg2+ on MSC immunomodulatory properties, cell proliferation rates, expression of NFκB and STAT-3, production of IL-1β, IL-6, TGF-β, IL-10, PGE2 and NO, and TRPM7 expression...
February 13, 2018: Journal of Nutritional Biochemistry
Genglong Liu, Haijin Lv, Yuling An, Xuxia Wei, Xiaomeng Yi, Huimin Yi
The aim of the present study was topreliminarily visualize the distribution of humanumbilical cord‑derivedmesenchymal stem cells (hUC‑MSCs) in treating acute lung injury (ALI) using a targeted fluorescent technique. Anovel fluorescent molecule probe was first synthesized via the specific binding of antigen and antibody in vitro to label the hUC‑MSCs. Two groups of mice, comprising a normal saline (NS)+MSC group and lipopolysaccharide (LPS)+MSC group, were subjected to optical imaging. At 4 h following ALI mouse model construction, the labeled hUC‑MSCs were transplanted into the mice in the NS+MSC group and LPS+MSC group by tail vein injection...
May 2018: International Journal of Molecular Medicine
Yuanmin Li, Jingping Liu, Guangneng Liao, Jie Zhang, Younan Chen, Lan Li, Li Li, Fang Liu, Bo Chen, Gang Guo, Chengshi Wang, Lichuan Yang, Jingqiu Cheng, Yangrong Lu
Diabetic nephropathy (DN) is a major complication of diabetes and represents the leading cause of end-stage renal disease. Mesenchymal stem cell (MSC) treatment has been demonstrated to be effective in DN models by reducing albuminuria and attenuating glomerular injury; however, limited in-depth understanding of the underlying mechanism and a lack of clinical trials hinders its clinical use. Additionally, most of these experimental studies were conducted on the advanced stage of nephropathy, which is difficult to reverse and consequently showed limited therapeutic efficacy...
February 16, 2018: International Journal of Molecular Medicine
Xiangxiao Li, Weihong Sun, Wenda Xi, Weili Shen, Tong Wei, Wendong Chen, Pingjin Gao, Qun Li
Skin mesenchymal stem cells (S-MSCs) revealed an important immunomodulatory activity to markedly suppress the formation of the atherosclerosis (AS) plaque by modulating macrophages, and also inhibit the development of experimental autoimmune encephalomyelitis (EAE) by regulating T helper 17 (Th17) cell differentiation. Macrophages and Th17 cells play important roles in hypertension. However, it remains unclear whether S-MSCs are capable of improving angiotensin (AngII)-induced hypertension by acting on inflammatory cells...
February 23, 2018: Biochemical and Biophysical Research Communications
Yu Li, Xin Gao, Jinbing Wang
Conditioned media (CM) from mesenchymal stem cells (MSCs) contains various cytokines, growth factors and microRNAs, which may serve important roles in modulating the inflammatory process. However, the effect of MSC-CM on inflammatory bone loss remains unknown. The present study investigated the effects of conditioned media from human adipose-derived mesenchymal stem cells (AMSC-CM) on the prevention of lipopolysaccharide (LPS)-mediated bone loss in mice. To investigate the underlying mechanisms of this effect, the effects of AMSC-CM on serum levels of inflammation-associated cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and IL-10] in LPS-treated mice, in addition to their mRNA expression in LPS-treated macrophages, was investigated...
February 2018: Experimental and Therapeutic Medicine
Elena Redondo-Castro, Catriona J Cunningham, Jonjo Miller, Helena Brown, Stuart M Allan, Emmanuel Pinteaux
BACKGROUND: Mesenchymal stem cells (MSCs) are one of the most promising candidates for the treatment of major neurological disorders. Desirable therapeutic properties of MSCs include reparative and regenerative potential but, despite their proven safety, the efficacy of MSCs remains controversial. Therefore, it is essential to optimise culture protocols to enhance the therapeutic potential of the MSC secretome. Here we aimed to: assess the increase in secretion of cytokines that may induce repair, regeneration, or immunomodulation when cultured in three dimensions; study the effect of interleukin (IL)-1 priming on two- (2D) and three-dimensional (3D) cultures of MSC; and evaluate the potential use of the modified secretome using microglial-MSC co-cultures...
January 17, 2018: Stem Cell Research & Therapy
Q H Chen, R Q Zheng, H L Wang, Y Yang, H B Qiu
Objective: To explore the role and mechanism of mesenchymal stem cell (MSC) in modulating human pulmonary microvascular endothelial cell (HPMECs) permeability via hepatocyte growth factor (HGF). Methods: The study introduced a co-cultured model between HPMECs and human mesenchymal stem cell conditioned media (MSC-CM) collected from MSCs after 24 h hypoxia culture, and meanwhile HGF was neutralized in MSC-CM by anti-HGF antibody respectively, followed by lipopolysaccharide (LPS) stimulation. Finally, the following measurements were performed: the permeability of HPMECs, the protein expression of vascular endothelial cadherin (VE-cadherin), Occludin in HPMECs by Western blot, HPMECs apoptosis by Annexin V-FITC/PI and HPMECs proliferation by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di- phenytetrazoliumromide(MTT)...
November 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
Chikako Morioka, Motohiro Komaki, Atsuko Taki, Izumi Honda, Naoki Yokoyama, Kengo Iwasaki, Sachiko Iseki, Tomohiro Morio, Ikuo Morita
Background: Periventricular leukomalacia (PVL) is a type of multifactorial brain injury that causes cerebral palsy in premature infants. To date, effective therapies for PVL have not been available. In this study, we examined whether mesenchymal stem cells (MSCs) possess neuroprotective property in a lipopolysaccharide (LPS)-induced neonatal rat PVL-like brain injury. Methods: Human umbilical cord-derived MSCs (UCMSCs) were used in this study. Four-day-old rats were intraperitoneally injected with LPS (15 mg/kg) to cause the PVL-like brain injury and were treated immediately after the LPS-injection with UCMSCs, conditioned medium prepared from MSCs (UCMSC-CM) or interferon-gamma (IFN-γ)-pretreated MSC (IFN-γ-UCMSC-CM)...
2017: Inflammation and Regeneration
Maria C Naskou, Natalie A Norton, Ian B Copland, Jacques Galipeau, John F Peroni
Platelet lysate (PL) has been extensively used for the laboratory expansion of human mesenchymal stem cells (MSC) in order to avoid fetal bovine serum (FBS) which has been associated with immune-mediated host reactions and transmission of bovine-origin microbial contaminants. Before suggesting the routine use of PL for MSC culture, we wanted to further investigate whether PL alone might trigger inflammatory responses when exposed to reactive white blood cells such as monocytes. Our objectives were to evaluate the inflammatory profile of equine monocytes cultured with equine PL (ePL) and to determine if ePL can modulate the expression of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated monocytes...
January 2018: Veterinary Immunology and Immunopathology
Jennifer M Cassano, Lauren V Schnabel, Margaret B Goodale, Lisa A Fortier
Mesenchymal stem cells (MSCs) have the therapeutic potential to treat a variety of inflammatory and degenerative disease processes, however the effects of the tissue environment on MSCs have been overlooked. Our hypothesis was that the immunomodulatory function of MSCs would be impaired by TLR4 stimulation or exposure to inflammatory macrophages, whereas their immunosuppressive properties would be enhanced by TLR3 stimulation. MSCs were exposed to polyinosinic:polycytidylic acid (poly I:C) to stimulate TLR3 receptors or lipopolysaccharide (LPS) to stimulate TLR4 receptors...
January 2018: Veterinary Immunology and Immunopathology
Guan Wang, Kai Cao, Keli Liu, Yueqing Xue, Arthur I Roberts, Fengying Li, Yanyan Han, Arnold B Rabson, Ying Wang, Yufang Shi
Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI...
December 13, 2017: Cell Death and Differentiation
Tzuhua Lin, Jukka Pajarinen, Akira Nabeshima, Laura Lu, Karthik Nathan, Eemeli Jämsen, Zhenyu Yao, Stuart B Goodman
BACKGROUND: Mesenchymal stem cells (MSCs) are capable of immunomodulation and tissue regeneration, highlighting their potential translational application for treating inflammatory bone disorders. MSC-mediated immunomodulation is regulated by proinflammatory cytokines and pathogen-associated molecular patterns such as lipopolysaccharide (LPS). Previous studies showed that MSCs exposed to interferon gamma (IFN-γ) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) synergistically suppressed T-cell activation...
December 6, 2017: Stem Cell Research & Therapy
Chung-Ming Chen, Willie Lin, Liang-Ti Huang, Hsiu-Chu Chou
Pulmonary hypertension is a critical problem in infants with bronchopulmonary dysplasia. This study determined the therapeutic effects of human mesenchymal stem cells (MSCs) on pulmonary hypertension in an animal model. Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on gestational days 20 and 21. The pups were randomly assigned to two treatment conditions: room air (RA) or an O2-enriched atmosphere. On postnatal day 5, they were intratracheally transplanted with human MSCs (3 × 10(5) and 1 × 10(6) cells) in 0...
October 10, 2017: Oncotarget
Zili Zhang, Wenfei Li, Zhizhi Heng, Jing Zheng, Puyuan Li, Xin Yuan, Wenkai Niu, Changqing Bai, Huiying Liu
ALI/ARDS remain the main reason of morbidity and mortality in the critically ill. Studies have indicated that human umbilical cord mesenchymal stem cells (hUC-MSCs) can be useful in the treatment of ALI/ARDS. Sphingosine-1-phosphate (S1P) and its analog FTY720 significantly reduce lipopolysaccharide (LPS)-induced lung edema and inflammatory lung injury. This study aimed to assess the therapeutic effects of hUC-MSCs combined with FTY720 in an LPS-induced murine model of ALI. Eight-week-old female C57BL/6 mice were divided into a normal control group, an LPS group, an hUC-MSC group, an FTY720 group, and an hUC-MSCs+FTY720 group randomly...
September 29, 2017: Oncotarget
Xiaoya Sun, Haojie Hao, Qingwang Han, Xiaoyan Song, Jiejie Liu, Liang Dong, Weidong Han, Yiming Mu
BACKGROUND: Insulin resistance is one of the most common and important pathological features of type 2 diabetes (T2D). Recently, insulin resistance is increasingly considered to be associated with systemic chronic inflammation. Elevated levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in blood are predictive indicators of the development of T2D. Mesenchymal stem cell (MSC)-based therapies have been proven to have potential immunomodulation and anti-inflammatory properties through their paracrine effects; however, the mechanism for the anti-inflammatory effect of MSCs in enhancing insulin sensitivity is still uncertain...
November 2, 2017: Stem Cell Research & Therapy
Heidi L Reesink, Ryan M Sutton, Carolyn R Shurer, Ryan P Peterson, Julie S Tan, Jin Su, Matthew J Paszek, Alan J Nixon
BACKGROUND: Mesenchymal stromal cells (MSCs) can be used intra-articularly to quell inflammation and promote cartilage healing; however, mechanisms by which MSCs mitigate joint disease remain poorly understood. Galectins, a family of β-galactoside binding proteins, regulate inflammation, adhesion and cell migration in diverse cell types. Galectin-1 and galectin-3 are proposed to be important intra-articular modulators of inflammation in both osteoarthritis and rheumatoid arthritis. Here, we asked whether equine bone marrow-derived MSCs (BMSCs) express higher levels of galectin-1 and -3 relative to synovial fibroblasts and chondrocytes and if an inflammatory environment affects BMSC galectin expression and motility...
November 2, 2017: Stem Cell Research & Therapy
Chenfei Wang, Dan Lv, Xiaobin Zhang, Zhu-Ang Ni, Xiaofan Sun, Changqing Zhu
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening inflammatory conditions with no effective pharmacological treatment. Previous studies suggested that mesenchymal stromal/stem cell (MSC) infusion resulted in better survival in mouse ALI models and presented low toxicity in human subjects. Therefore, in this study, we investigated the possibility of treating a murine model of ALI using MSCs with constant interleukin-10 overexpression (IL-10-MSC) by retroviral infection...
October 26, 2017: DNA and Cell Biology
Zunpeng Liu, Xue Yuan, Min Liu, Gabriela Fernandes, Yejia Zhang, Shuting Yang, Ciprian N Ionita, Shuying Yang
Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process...
September 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hualing Wang, Ruiqiang Zheng, Qihong Chen, Jun Shao, Jiangquan Yu, Shuling Hu
BACKGROUND: Mesenchymal stem cells microvesicles (MSC-MVs) stabilize endothelial barrier function in acute lung injury (ALI); however, the detailed mechanism remains to be further defined. Hepatocyte growth factor (HGF), which is derived from MSC-MVs, might have a key role in the restoration of endothelial barrier function by MSC-MVs. METHODS: MSCs with lentiviral vector-mediated HGF gene knockdown (siHGF-MSC) were generated. A co-culture model of pulmonary microvascular endothelial cells and MSC-MVs collected from MSCs or siHGF-MSCs after 24 h of hypoxic culture was utilized...
September 29, 2017: Stem Cell Research & Therapy
P Padmini S J Khedoe, Stan de Kleijn, Annemarie M van Oeveren-Rietdijk, Jaap J Plomp, Hetty C de Boer, Melissa van Pel, Patrick C N Rensen, Jimmy F P Berbée, Pieter S Hiemstra
BACKGROUND: COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice...
2017: PloS One
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