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inflammatory bowl disease

Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Regan C Manayan, Bruce A Bunnell
BACKGROUND: The therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur...
March 13, 2018: Journal of Neuroinflammation
Nathan Karin, Hila Razon
Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11...
February 12, 2018: Cytokine
Yuqian Yang, Yuexia Liao, Yan Ma, Weijuan Gong, Guoqiang Zhu
Adherent-invasive Escherichia coli (AIEC) has recently attracted more attention because it is closely related to the pathogenicity of human inflammatory bowel disease (IBD). AIEC possesses a multitude of virulence factors. Considering these virulence factors belonging to various virulence groups, including adhesins, invasins, toxins, protectins, and siderophore-mediated iron acquisition, this review summarizes the current knowledge of how the major virulence factors assisting in AIEC survive in, adhere to, and invade host cells...
November 2017: Applied Microbiology and Biotechnology
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
October 2017: Stem Cells
Julia Tcw, Minghui Wang, Anna A Pimenova, Kathryn R Bowles, Brigham J Hartley, Emre Lacin, Saima I Machlovi, Rawan Abdelaal, Celeste M Karch, Hemali Phatnani, Paul A Slesinger, Bin Zhang, Alison M Goate, Kristen J Brennand
Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state...
August 8, 2017: Stem Cell Reports
Johannes Hausmann, Renate Schmelz, Jens Walldorf, Natalie Filmann, Stefan Zeuzem, Jörg G Albert
BACKGROUND: Patients are at increased risk of disease recurrence after surgical treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown. METHODS: This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included...
April 21, 2017: Scandinavian Journal of Gastroenterology
Niloofar Farhang, Jonathan M Brunger, Joshua D Stover, Pratiksha I Thakore, Brandon Lawrence, Farshid Guilak, Charles A Gersbach, Lori A Setton, Robby D Bowles
Musculoskeletal diseases have been associated with inflammatory cytokine action, particularly action by TNF-α and IL-1β. These inflammatory cytokines promote apoptosis and senescence of cells in diseased tissue and extracellular matrix breakdown. Stem cell-based therapies are being considered for the treatment of musculoskeletal diseases, but the presence of these inflammatory cytokines will have similar deleterious action on therapeutic cells delivered to these environments. Methods that prevent inflammatory-induced apoptosis and proinflammatory signaling, in cell and pathway-specific manners are needed...
August 2017: Tissue Engineering. Part A
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
Talkea Schmidt, Nadine Lorenz, Verena Raker, Sonja Reißig, Ari Waisman, Benno Weigmann, Kerstin Steinbrink
Tolerance to environmental antigens that encounter the organism at interfaces like skin or gut prevents deleterious systemic immune responses. The aim of this study was to analyze whether and how low doses of haptens, by entry through the skin or gastrointestinal tract, affect the outcome of the predominantly Th1/Th17-mediated 2,4,6-trinitro-benzenesulfonic acid-induced colitis, which mimics an autoimmune bowl disease in man. Epicutaneous and oral applications of low doses of the allergen resulted in the induction of low-zone tolerance (LZT) and protected from colitis development, demonstrated by a significantly reduced inflammatory response of the gut in vivo...
September 2016: Journal of Investigative Dermatology
Amy L Strong, Annie C Bowles, Rachel M Wise, Joseph P Morand, Maria F Dutreil, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis is an autoimmune disease that affects the white matter of the central nervous system and involves inflammation and demyelination. The recent advances in our understanding of adipose-derived stromal/stem cells (ASCs) and the utilization of these cells in clinical settings to treat diseases have made it essential to identify the most effective ASCs for therapy. Studies have not yet investigated the impact of obesity on the therapeutic efficacy of ASCs. Obesity is characterized by adipocyte hyperplasia and hypertrophy and can extend to metabolic and endocrine dysfunction...
March 2016: Stem Cells
Barbara P Barna, Matthew McPeek, Anagha Malur, Michael B Fessler, Christopher J Wingard, Larry Dobbs, Kathryn M Verbanac, Mark Bowling, Marc A Judson, Mary Jane Thomassen
We established a murine model of multiwall carbon nanotube (MWCNT)-induced chronic granulomatous disease, which resembles human sarcoidosis pathology. At 60 days after oropharyngeal MWCNT instillation, bronchoalveolar lavage (BAL) cells from wild-type mice exhibit an M1 phenotype with elevated proinflammatory cytokines and reduced peroxisome proliferator-activated receptor γ (PPARγ)-characteristics also present in human sarcoidosis. Based upon MWCNT-associated PPARγ deficiency, we hypothesized that the PPARγ target gene, ATP-binding cassette (ABC) G1, a lipid transporter with antiinflammatory properties, might also be repressed...
June 2016: American Journal of Respiratory Cell and Molecular Biology
Roger B Ruggeri, Leonard Buckbinder, Scott W Bagley, Philip A Carpino, Edward L Conn, Matthew S Dowling, Dilinie P Fernando, Wenhua Jiao, Daniel W Kung, Suvi T M Orr, Yingmei Qi, Benjamin N Rocke, Aaron Smith, Joseph S Warmus, Yan Zhang, Daniel Bowles, Daniel W Widlicka, Heather Eng, Tim Ryder, Raman Sharma, Angela Wolford, Carlin Okerberg, Karen Walters, Tristan S Maurer, Yanwei Zhang, Paul D Bonin, Samantha N Spath, Gang Xing, David Hepworth, Kay Ahn, Amit S Kalgutkar
Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option. Herein, we present the design, synthesis, and preclinical evaluation of N1-substituted-6-arylthiouracils as potent and selective inhibitors of MPO. Inhibition proceeded in a time-dependent manner by a covalent, irreversible mechanism, which was dependent upon MPO catalysis, consistent with mechanism-based inactivation...
November 12, 2015: Journal of Medicinal Chemistry
R E Burgell, A K Asthana, P R Gibson
Ongoing troublesome bowel symptoms despite quiescent inflammatory disease are a frequent management challenge when caring for patients with inflammatory bowel disease (IBD). Even when active disease has been excluded the prevalence of residual gastrointestinal symptoms is surprisingly high and the cause often obscure. The presence of a concurrent functional disorder such as irritable bowel syndrome (IBS) is associated with worse quality of life, worse physical functioning, higher prevalence of anxiety and greater health care utilization...
December 2015: Minerva Gastroenterologica e Dietologica
Jiazhuo Wang, John D MacKenzie, Rageshree Ramachandran, Danny Z Chen
Identifying neutrophils lays a crucial foundation for diagnosing acute inflammation diseases. But, such computerized methods on the commonly used H&E staining histology tissue images are lacking, due to various inherent difficulties of identifying cells in such image modality and the challenge that a considerable portion of neutrophils do not have a "textbook" appearance. In this paper, we propose a new method for identifying neutrophils in H&E staining histology tissue images. We first segment the cells by applying iterative edge labeling, and then identify neutrophils based on the segmentation results by considering the "context" of each candidate cell constructed by a new Voronoi diagram of clusters of other neutrophils...
2014: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
Annie C Bowles, Brittni A Scruggs, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease that presents after an auto-reactive immune response against constituents of the central nervous system. Demyelination, inflammation, and white matter lesions are all hallmarks of this disease. Clinical research supports the use of mesenchymal stem cells (MSCs) as therapy for MS to ameliorate symptoms and pathology. MSCs can be isolated from multiple tissues, including adipose and bone marrow, and are able to migrate to sites of pathology, release anti-inflammatory factors, and provide immunomodulatory and neuroprotective effects once administered...
2014: Methods in Molecular Biology
Meaghan R Bowling, Dongqi Xing, Akash Kapadia, Yiu-Fai Chen, Alexander J Szalai, Suzanne Oparil, Fadi G Hage
OBJECTIVE: 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. APPROACH AND RESULTS: Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs)...
July 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Jacques Moreau
Extremely variable in their clinical expression, inflammatory bowl diseases evolve by flare-ups interspersed with phases of remission. Complications can be severe, sometimes requiring surgery. While treatments have evolved considerably, therapeutic patient education plays an important role in the therapeutic approach.
March 2014: Revue de L'infirmière
Xiujuan Zhang, Annie C Bowles, Julie A Semon, Brittni A Scruggs, Shijia Zhang, Amy L Strong, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS), characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs) for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE), a murine model of MS...
2014: PloS One
Fuat Hakan Saner, Knut Nowak, Dieter Hoyer, Peter Rath, Ali Canbay, Andreas Paul, Michael Koldehoff, Ahmet Elmaağaclı
BACKGROUND: Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival...
2014: BMC Gastroenterology
Brittni A Scruggs, Xiujuan Zhang, Annie C Bowles, Peter A Gold, Julie A Semon, Jeanne M Fisher-Perkins, Shijia Zhang, Ryan W Bonvillain, Leann Myers, Su Chen Li, Allan V Kalueff, Bruce A Bunnell
Globoid cell leukodystrophy (GLD) is a common neurodegenerative lysosomal storage disorder caused by a deficiency in galactocerebrosidase (GALC), an enzyme that cleaves galactocerebroside during myelination. Bone marrow transplantation has shown promise when administered to late-onset GLD patients. However, the side effects (e.g., graft vs. host disease), harsh conditioning regimens (e.g., myelosuppression), and variable therapeutic effects make this an unsuitable option for infantile GLD patients. We previously reported modest improvements in the twitcher mouse model of GLD after intracerebroventricular (ICV) injections of a low-dose of multipotent stromal cells (MSCs)...
August 2013: Stem Cells
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