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Xiaolin Xie, Hanhan Liu, Jinhua Wu, Yun Chen, Zhui Yu, Natalia De Isla, Xiaohua He, Yinping Li
BACKGROUND: Mesenchymal stem cells (MSC) have been shown to have potent immunoregulatory effects. They are able to mitigate inflammation in many contexts of immune disorders, including autoimmune diseases and graft-versus-host disease (GVHD). Endotoxemia can induce systematic inflammation in the body. In this study, we try to investigate whether MSC can attenuate inflammation in models of LPS-induced endotoxemia. METHODS: Bone marrow MSC (BMSC) were isolated and expanded from rats of 4~6-week age...
2017: Bio-medical Materials and Engineering
Pei-Lun Lai, Hsuan Lin, Shang-Fu Chen, Shang-Chih Yang, Kuo-Hsuan Hung, Ching-Fang Chang, Hsiang-Yi Chang, Frank Leigh Lu, Yi-Hsuan Lee, Yu-Chuan Liu, Hsiao-Chun Huang, Jean Lu
Human mesenchymal stromal/stem cells (MSCs) are multipotent and currently undergoing hundreds of clinical trials for disease treatments. To date, no studies have generated induced MSCs from skin fibroblasts with chemicals or growth factors. Here, we established the first chemical method to convert primary human dermal fibroblasts into multipotent, induced MSC-like cells (iMSCs). The conversion method uses a defined cocktail of small molecules and growth factors, and it can achieve efficient conversion with an average rate of 38% in 6 days...
March 17, 2017: Scientific Reports
Natalie Fernandez, Heather Renna, Lauren McHugh, Katie Mazolkova, William Crugnola, Jodi F Evans
Mesenchymal progenitor cell characteristics that can identify progenitor populations with specific functions in immunity are actively being investigated. Progenitors from bone marrow and adipose tissue regulate the macrophage (MΦ) inflammatory response by promoting the switch from an inflammatory to an anti-inflammatory phenotype. Conversely, mesenchymal progenitors from the mouse aorta (mAo) support and contribute to the MΦ response under inflammatory conditions. We used cell lines with purported opposing immune-regulatory function, a bone marrow derived mesenchymal progenitor cell line (D1) and a mouse aorta derived mesenchymal progenitor cell line (mAo)...
2017: Stem Cells International
Zahra Khosrowpour, Seyed Mahmoud Hashemi, Samira Mohammadi-Yeganeh, Sara Soudi
Recent studies have demonstrated the influential role of microbial stimulus in characteristics and immunomodulatory effects of mesenchymal stem cells (MSCs). Due to the migration of MSCs to infection site, it is of importance to understand the interaction of microbial ligands with MSCs in order to clarify the positive or negative role of MSCs in the control of infection. In this research, we assess leishmanial soluble antigen (LSA)-primed MSCs on macrophage immune responses to lipopolysaccharide (LPS). For this purpose, the effects of both conditioned media (CM) and cell-cell contact of LSA primed MSCs were determined on macrophage responses to LPS...
February 8, 2017: Journal of Cellular Biochemistry
Ieva Bruzauskaite, Jovile Raudoniute, Jaroslav Denkovskij, Edvardas Bagdonas, Sandra Meidute-Abaraviciene, Vaida Simonyte, Daiva Bironaite, Almantas Siaurys, Eiva Bernotiene, Ruta Aldonyte
Studies of lung diseases in vitro often rely on flat, plastic-based monocultures, due to short lifespan of primary cells, complicated anatomy, lack of explants, etc. We hereby present a native 3D model with cues for repopulating epithelial cells. Abilities of mesenchymal stem cells (MSC) to modulate bacterial lipopolysaccharide (LPS) and cigarette smoke-induced injury to pulmonary epithelium were tested in our model. Post-mortem human lung tissue was sliced, cut and decellularized. Resulting matrix pads were reseeded with pulmonary epithelium (A549 line)...
February 2017: Cytotechnology
Nicole Herzmann, Achim Salamon, Tomas Fiedler, Kirsten Peters
Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC...
January 1, 2017: Experimental Cell Research
Yarúa Jaimes, Yahaira Naaldijk, Kerstin Wenk, Christiane Leovsky, Frank Emmrich
Microglia cells are the central nervous system immune cells and have been pointed out as the main mediators of the inflammation leading to neurodegenerative disorders. Mesenchymal stromal cells (MSCs) are a heterogeneous population of cells with very high self-renewal properties and uncomplicated in vitro culture. Research has shown that MSCs have the capacity to induce tissue regeneration and reduce inflammation. Studies demonstrated that MSCs have complex paracrine machineries involving shedding of cell-derived microvesicles (MVs), which entail part of the regulatory and regenerative activity of MSCs, as observed in animal models...
March 2017: Stem Cells
William H Wheat, Lyndah Chow, Jade N Kurihara, Daniel P Regan, Jonathan W Coy, Tracy L Webb, Steven W Dow
Mesenchymal stem cells (MSC) represent a readily accessible source of cells with potent immune modulatory activity. MSC can suppress ongoing inflammatory responses by suppressing T cell function, while fewer studies have examined the impact of MSC on dendritic cell (DC) function. The dog spontaneous disease model represents an important animal model with which to evaluate the safety and effectiveness of cellular therapy with MSC. This study evaluated the effects of canine MSC on the activation and maturation of canine monocyte-derived DC, as well as mechanisms underlying these effects...
February 15, 2017: Stem Cells and Development
Xin Zhao, Xiaolei Shi, Zhiheng Zhang, Hucheng Ma, Xianwen Yuan, Yitao Ding
BACKGROUND: The imbalance of immunity is an important pathogenesis of acute liver failure (ALF). Neutrophils are the hallmark of acute inflammation, which have an essential role in immune regulation. Mesenchymal stem cell (MSC) transplantation is a promising therapy in ALF treatment. Recent studies indicated a considerable connection between MSCs and neutrophils in immune regulation. AIM: To investigate changes in neutrophils in ALF rats after MSC transplantation, and to explore the therapeutic effect and mechanism of the combined treatment with MSC transplantation and neutrophil depletion in ALF...
December 2016: Clinics and Research in Hepatology and Gastroenterology
Hao Ou, Shangping Zhao, Yue Peng, Xuefei Xiao, Qianlu Wang, Huaizeng Liu, Xianzhong Xiao, Mingshi Yang
Mesenchymal stem cells (MSCs) have been reported to regulate the systemic inflammatory response and sepsis-induced immunologic injury pre-clinically. However, whether MSCs from different sources elicit identical effects remains to be elucidated. The present study compared the effect of bone marrow‑derived MSCs (BMSCs) and adipose tissue-derived MSCs (ADMSCs) in a murine model of lipopolysaccharide (LPS)‑induced sepsis. SPF BALB/c mice were induced with an injection of LPS (10 mg/kg; 1 mg/ml) via the tail vein...
October 2016: Molecular Medicine Reports
Guang-Ping Ruan, Xiang Yao, Ju-Fen Liu, Jie He, Zi-An Li, Jian-Yong Yang, Rong-Qing Pang, Xing-Hua Pan
BACKGROUND: The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. METHODS: Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group...
August 24, 2016: Stem Cell Research & Therapy
Andreia Ribeiro, Thomas Ritter, Matthew Griffin, Rhodri Ceredig
Human bone marrow-derived mesenchymal stromal/stem cells (MSC) have well-documented modulatory effects on multiple immune cell types. Although these effects are linked to their therapeutic benefit in diverse diseases, a reliable, quantitative assay of the immunomodulatory potency of individual human MSC preparations is lacking. The aims of this study were to develop an optimised rapid turnaround, flow cytometry-based whole-blood assay to monitor MSC potency and to validate its application to MSC immunomodulation...
September 2016: Immunology Letters
Sun Hwa Kim, Amitabh Das, Jin Choul Chai, Bert Binas, Mi Ran Choi, Kyoung Sun Park, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Due to their multipotentiality and immunomodulation, human mesenchymal stem cells (hMSCs) are widely studied for the treatment of degenerative and inflammatory diseases. Transplantation of hMSCs to damaged tissue is a promising approach for tissue regeneration. However, the physiological mechanisms and regulatory processes of MSC trafficking to injured tissue are largely unexplored. Here, we evaluated the gene expression profile and migratory potential of hMSCs upon stimulation with the TLR4 ligand lipopolysaccharide (LPS)...
2016: Scientific Reports
Xiao Li, Lingying Liu, Jing Yang, Yonghui Yu, Jiake Chai, Lingyan Wang, Li Ma, Huinan Yin
Mesenchymal stem cell (MSC)-derived exosomes have diverse functions in regulating wound healing and inflammation; however, the molecular mechanism of human umbilical cord MSC (hUCMSC)-derived exosomes in regulating burn-induced inflammation is not well understood. We found that burn injury significantly increased the inflammatory reaction of rats or macrophages exposed to lipopolysaccharide (LPS), increased tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) levels and decreased IL-10 levels. hUCMSC-exosome administration successfully reversed this reaction...
June 2016: EBioMedicine
Min Young Noh, Su Min Lim, Ki-Wook Oh, Kyung-Ah Cho, Jinseok Park, Kyung-Suk Kim, Su-Jung Lee, Min-Soo Kwon, Seung Hyun Kim
: The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-β (TGF-β) levels in mesenchymal stromal cells (MSCs) could be used as potential biological markers to predict the effectiveness of autologous MSC therapy in patients with amyotrophic lateral sclerosis. However, the underlying mechanism of TGF-β in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-β that is involved in MSC effectiveness, especially focusing on microglia functional properties that play a pivotal role in neuroinflammation...
November 2016: Stem Cells Translational Medicine
Franka Luk, Samantha F H de Witte, Sander S Korevaar, Marieke Roemeling-van Rhijn, Marcella Franquesa, Tanja Strini, Sandra van den Engel, Madhusudhana Gargesha, Debashish Roy, Frank J M F Dor, Edwin M Horwitz, Ron W F de Bruin, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn
Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of action and the therapeutic components of MSC. Such knowledge allows better identification of diseases that are responsive to MSC treatment, optimization of the MSC product, and development of therapy based on functional components of MSC...
September 15, 2016: Stem Cells and Development
Hsiu-Chu Chou, Willie Lin, Chung-Ming Chen
Intra-amniotic injection of lipopolysaccharide (LPS) induces pulmonary hypertension in newborn rats. This study was designed to test whether human mesenchymal stem cells (MSCs) reduce pulmonary hypertension and alleviate cardiac hypertrophy in prenatal LPS-treated rats. Pregnant Sprague-Dawley rats were injected intraperitoneally with LPS (0.5 mg/kg per day) or untreated on gestational days 20 and 21. Human MSCs (3×10(5) cells and 1×10(6) cells) in 0.03 mL of normal saline (NS) were transplanted intratracheally on postnatal day 5...
October 2016: Clinical and Experimental Pharmacology & Physiology
Bruno Sangiorgi, Helder Teixeira De Freitas, Josiane Lilian Dos Santos Schiavinato, Vitor Leão, Rodrigo Haddad, Maristela Delgado Orellana, Vitor Marcel Faça, Germano Aguiar Ferreira, Dimas Tadeu Covas, Marco Antônio Zago, Rodrigo Alexandre Panepucci
Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6...
July 2016: Cytotherapy
Jibin Han, Xiaomin Lu, Lijuan Zou, Xiuping Xu, Haibo Qiu
Mesenchymal stem cells (MSCs) represent a promising approach for the treatment of acute respiratory distress syndrome (ARDS). However, their low efficiency in homing to injured lung tissue limits their therapeutic effect. Prostaglandin E2 (PGE2) biosynthesis substantially enhances the inflammatory response of the tissue. Moreover, it also facilitates the migration of MSCs by activating the E-prostanoid 2 (EP2) receptor in vitro. Given these observations, it would seem reasonable that PGE2 might act as a chemokine to promote the migration of MSCs through activation of the EP2 receptor...
August 2016: Human Gene Therapy
Hsiu-Chu Chou, Yuan-Tsung Li, Chung-Ming Chen
BACKGROUND: Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia. METHODS: Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on Gestational Days 20 and 21. Human MSCs (3×10(5) and 1×10(6) cells) in 0...
2016: American Journal of Translational Research
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