Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis
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Tendon Fibroblasts
Ann Rheum Dis: first published as 10.1136/ard.46.5.385 on 1 May 1987. Downloaded from Annals of the Rheumatic Diseases, 1987; 46, 385-390 Isolation and growth characteristics of adult human tendon fibroblasts M D CHARD, J K WRIGHT, AND B L HAZLEMAN From the Rheumatology Research Unit, Addenbrooke's Hospital, Hills Road, Cambridge SUMMARY An explant method for the isolation of fibroblasts from adult human tendon is described. Cells were successfully isolated from 22 out of 27 common biceps tendons obtained from cadaveric donors (age range 11-83 years). The fibroblasts could be maintained in culture using standard methods and morphologically resembled those of synovial rather than dermal origin. Growth characteristics of 12 cell lines were assessed by deoxyribose nucleic acid (DNA) synthesis using [3H]thymidine incorporation in response to stimulation by fetal calf serum. Cells obtained separately from superficial and deep parts of the tendons produced almost identical responses. No significant reduction in growth response with increasing age was found when related to the age of the donor. Therefore this study did not show any age related defect in the short term tendon fibroblast replicative responses to serum. Key words: in vitro, DNA synthesis. copyright. Tendinous lesions are common, but their nature and other tissues such as skin. It is desirable to investi- any possible predisposing factors are not well gate adult human tendon fibroblasts directly. It was understood. They occur in middle life frequently thought that the culture of adult human tendon after only minor, if any, injury. The extent to which fibroblasts would be very difficult to achieve be- this reflects age related changes in tendon tissue is cause of the differentiated appearance of cells on uncertain. -
06. Baransel Saygi
Turkish Journal of Trauma & Emergency Surgery Ulus Travma Acil Cerrahi Derg 2008;14(2):103-109 The effect of dehydration and irrigation on the healing of Achilles tendon: an experimental study Dehidrasyon (kuruluk) ve irigasyonun (y›kama) Aflil tendon iyileflmesi üzerine etkileri: Deneysel çalıflma Baransel SA Y G I,1 Yakup YI L D I R I M,2 Cengiz ÇA B U K O ⁄ L U,3 Hasan KA R A,3 Saime Sezgin RA M A D A N,4 Tanıl ES E M E N L ‹ 5 BACKGROUND AMAÇ Air exposure is a factor that inhibits in vitro cellular prolifer- Hava teması tendonlarda canl›-d›fl› (in vitro) ortamda matriks ation and matrix synthesis in tendons. Aim of this experimen- sentezini ve hücre ilerlemesini azaltabilir ve hatta önleyebilir. tal study was to evaluate effect of dehydration and irrigation Bu çalıflmanın amacı, dehidrasyon ve irigasyonun Aflil tendon on healing of Achilles tendon. iyileflmesi üzerine etkisinin canl›-içi (in vivo) hayvan modeli METHODS üzerinde gösterilmesidir. Achilles tenotomy was done in forty-five Sprague-Dawley GEREÇ VE YÖNTEM rats. In control group, tendon was sutured immediately. In the K›rk befl adet Sprague-Dawley cinsi s›çan›n Aflil tenotomisi remaining two groups, the Achilles tendons were allowed to yapıldı. Kontrol grubunda, tendon hemen dikildi. Di¤er iki direct exposure of air. Irrigation of Achilles tendon was per- grubun cilt ve cilt altı dokuları ekarte edilerek Aflil tendon- formed in one of exposed groups, while irrigation was not larının do¤rudan hava ile teması sa¤landı. Bu gruplardan biri- done in other group. -
Endotrophin Triggers Adipose Tissue Fibrosis and Metabolic Dysfunction
ARTICLE Received 12 Sep 2013 | Accepted 21 Feb 2014 | Published 19 Mar 2014 DOI: 10.1038/ncomms4485 Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction Kai Sun1,*, Jiyoung Park1,2,*, Olga T. Gupta1, William L. Holland1, Pernille Auerbach3, Ningyan Zhang4, Roberta Goncalves Marangoni5, Sarah M. Nicoloro6, Michael P. Czech6, John Varga5, Thorkil Ploug3, Zhiqiang An4 & Philipp E. Scherer1,7 We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the ‘unhealthy’ adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer. 1 Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA. 2 Department of Biological Sciences, School of Life Sciences, Ulsan National Institute of Science and Technology, 50 UNIST street, Ulsan 689-798, Korea. -
Mesenchymal Stromal Cells and Fibroblasts Christine Ulrich1, Melanie L
Scienc e e & su s E i n T g f i o n Journal of Ulrich et al. J Tissue Sci Eng 2012, 3:1 l e e a r n i r n DOI: 10.4172/2157-7552.1000e109 u g o J ISSN: 2157-7552 Tissue Science & Engineering Editorial Open Access Mesenchymal Stromal Cells and Fibroblasts Christine Ulrich1, Melanie L. Hart1,2, Bernd Rolauffs3, Harald Abele4, Marco Götze5, Karin Benz6 and Wilhelm K. Aicher1,5* 1Center for Regenerative Biology and Medicine, University of Tübingen, Germany 2Department of Anesthesiology and Intensive Care, University of Tübingen Hospital, Tübingen, Germany 3BGU Trauma Center, Tübingen, Germany 4Department of Obstetrics and Gynaecology, UKT, University of Tübingen Hospital, Tübingen,Germany 5Department of Orthopaedic Surgery, University of Tübingen Hospital, Tübingen, Germany 6Department of Cell Biology, Regenerative Medicine II, NMI at University of Tübingen, Reutlingen, Germany Summary Adult mesenchymal stromal cells (MSC), also referred to as mesenchymal stem cells, were detected almost half a century ago in bone marrow and have been studied intensively in the last decade. Different aspects of MSC biology were explored and published. Studies pointed to their localization in different organs during development and in adulthood and described their characteristics in experimental or clinical investigations. Despite intensive research in the field and in sharp contrast to hematopoietic stem cells (HSC), it has become more and more clear that MSC lack a unique cell surface marker. MSC not only share cell surface markers with other types of cells, they also share many features with pericytes and fibroblasts, including their capability to differentiate into, for instance, osteoblasts or adipocytes. -
Effects of Collagen-Derived Bioactive Peptides and Natural Antioxidant
www.nature.com/scientificreports OPEN Efects of collagen-derived bioactive peptides and natural antioxidant compounds on Received: 29 December 2017 Accepted: 19 June 2018 proliferation and matrix protein Published: xx xx xxxx synthesis by cultured normal human dermal fbroblasts Suzanne Edgar1, Blake Hopley1, Licia Genovese2, Sara Sibilla2, David Laight1 & Janis Shute1 Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive efects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3–8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fbroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides signifcantly increased fbroblast elastin synthesis, while signifcantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive efects of the collagen peptides on these responses and on fbroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientifc, cell-based, rationale for the positive efects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fbroblast-derived extracellular matrices may follow their oral consumption. Te biophysical properties of the skin are determined by the interactions between cells, cytokines and growth fac- tors within a network of extracellular matrix (ECM) proteins1. Te fbril-forming collagen type I is the predomi- nant collagen in the skin where it accounts for 90% of the total and plays a major role in structural organisation, integrity and strength2. -
Cross-Tissue, Single-Cell Stromal Atlas Identifies Shared Pathological Fibroblast Phenotypes In
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.11.426253; this version posted January 12, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in 2 four chronic inflammatory diseases 3 Ilya Korsunsky1-5,15, Kevin Wei1,15, Mathilde Pohin6,15, Edy Y. Kim7,8,15, Francesca Barone9,15, Joyce 4 B. Kang1-5, Matthias Friedrich6, Jason Turner9, Saba Nayar9,10, Benjamin A. Fisher9,10, Karim Raza9,, 5 Jennifer L. Marshall9, Adam P. Croft9, Lynette M. Sholl11, Marina Vivero11, Ivan O. Rosas12, Simon J. 6 Bowman9,10, Mark Coles6, Andreas P. Frei13, Kara Lassen13, Andrew Filer9,10, Fiona Powrie6,16,*, 7 Christopher D. Buckley9,10,16,*, Michael B. Brenner1,7,16,*, Soumya Raychaudhuri1-5,14,16,17,* 8 1Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital and Harvard Medical School, 9 Boston, MA, USA. 10 2Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA. 11 3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA. 12 4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 13 5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 14 6Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, 15 University of Oxford, Oxford OX3 7FY, United Kingdom 16 7Harvard Medical School, Boston, MA 02115, USA 17 8Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA 18 9Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, 19 University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2WD, UK. -
Fibrosis in Human Adipose Tissue
ORIGINAL ARTICLE Fibrosis in Human Adipose Tissue: Composition, Distribution, and Link With Lipid Metabolism and Fat Mass Loss Adeline Divoux,1 Joan Tordjman,1 Danie`le Lacasa,2 Nicolas Veyrie,1,3 Danielle Hugol,1,4 Abdelhalim Aissat,1,3 Arnaud Basdevant,1,2 Miche`le Guerre-Millo,1 Christine Poitou,1,2 Jean-Daniel Zucker,1 Pierre Bedossa,1,5 and Karine Cle´ment1,2 OBJECTIVE—Fibrosis is a newly appreciated hallmark of the pathological alteration of human white adipose tissue (WAT). We investigated the composition of subcutaneous (scWAT) and hite adipose tissue (WAT) is the main energy omental WAT (oWAT) fibrosis in obesity and its relationship with repository in the body. It stores and mobi- metabolic alterations and surgery-induced weight loss. lizes, according to body demand, fatty acids RESEARCH DESIGN AND METHODS—Surgical biopsies for Wthat have been implicated in the development scWAT and oWAT were obtained in 65 obese (BMI 48.2 Ϯ 0.8 of insulin resistance. In turns, the phenotype and the kg/m2) and 9 lean subjects (BMI 22.8 Ϯ 0.7 kg/m2). Obese biology of WAT cellular components are altered by two subjects who were candidates for bariatric surgery were major processes: adipose cell hypertrophy and immune clinically characterized before, 3, 6, and 12 months after cells accumulation. Inflammation, reticulum endoplasmic surgery, including fat mass evaluation by dual energy X-ray stress, and hypoxia are part of the biologic alterations that absorptiometry. WAT fibrosis was quantified and character- ized using quantitative PCR, microscopic observation, and attract and retain inflammatory cells in WAT (1). -
Nomina Histologica Veterinaria, First Edition
NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria. -
Empowering Collagen Targeting for Diagnosis and Treatment of Human Conditions
EmpoweringEmpowering collagen collagen targetingtargeting for for diagnosis prognosis of fibrotic and treatment of Manka,SW. 2012 conditions.human conditions. 1 3Helix as a platform diagnostic company 2020 2022 2030 Innovative research reagent for Clinic histopathology providing Platform fibrotic prognostic detection of collagen damage best in class prognostic ability in within multi-disease states liver fibrosis (NAFLD, NASH) Strengthening IP portfolio with market Clinical histopathology AND Non-Invasive approaches serum testing and medical disrupting products while subsequently Analytic specific reagent to allow for fast imaging developing strong partnerships with world market access leading companies for commercialization Targeting impactful markets of IPF, kidney Focused on paired biopsy research and fibrosis, AMD, Keloids and cardiac fibrosis collaboration with clinical laboratories. in addition to fibrotic liver diseases. 2 Liver Fibrosis market is GROWING Fatty Liver Fibrotic Liver Healthy Liver Cirrhosis NAFLD NASH USA Epidemiology 328 Million 83 Million 16 Million 1.5 Million (2015) Predicted USA Epidemiology 360 Million 101 Million 27 Million 3.4 Million (2030) Estes,C. 2018 3 NASH Therapeutics are finishing clinical trials and are coming to market. • VK2809 Phase II • OCALIVA (OCA) • NDA Filed • $78,000/year current cost • $20,000 predicted • Resmetirom Phase III • 23% respond to treatment 16 Million NASH patients in the USA * $20,000 • $320 Billion Annual Cost for treatable market Aramchol Phase III/IV 4 Stratification of patient population is needed to reduce unnecessary therapeutic intervention. • Progression of NAFL and 100% NASH is variable patient to NAFLD patient. 33% • Prediction of the progression can modify the Fibrosis Progression 20% disease intervention and treatment. Rapid Fibrosis • No product on the market Progression (stage 0 to stage today is equipped for 3/4 over 5.9 years) prognosis of liver fibrosis Singh, S. -
Skeletal Muscle – Fibrosis
Skeletal Muscle – Fibrosis Figure Legend: Figure 1 Skeletal muscle - Fibrosis in a male Harlan Sprague-Dawley rat from a subchronic study. Early change consists of increased perimysial deposits of pale eosinophilic material (immature collagen). Figure 2 Skeletal muscle - Fibrosis in a male Harlan Sprague-Dawley rat from a subchronic study. Note the perimysial proliferation of fibroblasts and early collagen deposition. Figure 3 Skeletal muscle - Fibrosis in a male Harlan Sprague-Dawley rat from a subchronic study (higher magnification of Figure 2). There is deposition of perimysial connective tissue and attenuation of several muscle fibers. Figure 4 Skeletal muscle - Fibrosis in a male F344/N rat from a chronic study. There is marked fibrosis with attenuation and loss of muscle bundles. 1 Skeletal Muscle – Fibrosis Comment: In skeletal muscle, the predominant histologic features of fibrosis are increased numbers of plump reactive fibroblasts with prominent vesiculated nuclei, and increased amounts of pale eosinophilic fibrillar material (collagen deposition) separating and surrounding adjacent myofibers (Figure 1, Figure 2, Figure 3, and Figure 4). Affected myofibers may or may not exhibit histologic features of atrophy, degeneration, necrosis, or regeneration. Fibrosis is the end result of a cascade of events that begins with tissue injury and inflammation and ends in permanent scar formation. When tissue is damaged, profibrotic cytokines, such as transforming growth factor beta, are released by the infiltrating inflammatory cells. These cytokines signal the fibroblasts to migrate into the affected region and to begin producing and remodeling the extracellular matrix. The stromal fibroblasts then begin producing cytokines, growth factors, and proteases that further trigger and uphold the inflammatory/profibrotic conditions. -
Human Dermal Fibroblast Manual
ZenBio, Inc. Human Dermal Fibroblast Manual INSTRUCTIONAL MANUAL ZBM0023.05 SHIPPING CONDITIONS Human Adult or Neonatal Dermal Fibroblast Cells Orders are delivered via Federal Express courier. All US and Canada orders are shipped via Federal Express Priority service and are usually received the next day. International orders are usually received in 3-4 days. Must be processed upon shipment receipt. STORAGE CONDITIONS Media: Short Term (30 days): 4°C 6 months -20°C Cells: Frozen: Vapor phase liquid nitrogen Live Plated: 37°C incubator All Zen-Bio Inc products are for research use only. Not approved for human or veterinary use or for use in diagnostic or clinical procedures. ORDERING INFORMATION AND TECHNICAL SERVICES ZenBio, Inc. 3200 East NC-54 Suite 100 PO Box 13888 Research Triangle Park, NC 27709 U.S.A. Telephone (919) 547-0692 Facsimile (FAX) (919) 547-0693 Toll free (continental US only) 1-866-ADIPOSE 1-(866)-234-7673 Electronic mail (e-mail) [email protected] World Wide Web http://www.zenbio.com THIS MANUAL IS SUITABLE FOR USE WITH THE FOLLOWING PRODUCTS: DF-F HUMAN DERMAL FIBROBLASTS DFN-F HUMAN NEONATAL DERMAL FIBROBLASTS DF-F-PS HUMAN DERMAL FIBROBLASTS FROM PSORIASIS DONOR DF-D-F HUMAN DERMAL FIBROBLASTS FROM TYPE 2 DIABETIC DONOR DF-1, DF-1-PRF DERMAL FIBROBLAST MEDIUM, - PHENOL RED FREE DFM-100 DERMAL FIBROBLAST CRYOPRESERVATION MEDIUM RV. 04.2016 Page 1 of 7 ZenBio, Inc. CONTENTS PAGE # Introduction/Precautions/Warranty 3 Catalog Items 4 Media Compositions 4 Plating and Expansion of Cryopreserved Cells 5 Frequently Asked Questions 6 Pathogen Testing 7 RV. -
Deciphering the Cellular Interplays Underlying Obesity-Induced Adipose Tissue Fibrosis
Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis Geneviève Marcelin, … , Adaliene V.M. Ferreira, Karine Clément J Clin Invest. 2019. https://doi.org/10.1172/JCI129192. Review Series Obesity originates from an imbalance between caloric intake and energy expenditure that promotes adipose tissue expansion, which is necessary to buffer nutrient excess. Patients with higher visceral fat mass are at a higher risk of developing severe complications such as type 2 diabetes and cardiovascular and liver diseases. However, increased fat mass does not fully explain obesity’s propensity to promote metabolic diseases. With chronic obesity, adipose tissue undergoes major remodeling, which can ultimately result in unresolved chronic inflammation leading to fibrosis accumulation. These features drive local tissue damage and initiate and/or maintain multiorgan dysfunction. Here, we review the current understanding of adipose tissue remodeling with a focus on obesity-induced adipose tissue fibrosis and its relevance to clinical manifestations. Find the latest version: https://jci.me/129192/pdf The Journal of Clinical Investigation REVIEW SERIES: MECHANISMS UNDERLYING THE METABOLIC SYNDROME Series Editor: Philipp E. Scherer Deciphering the cellular interplays underlying obesity- induced adipose tissue fibrosis Geneviève Marcelin,1 Ana Letícia M. Silveira,1,2 Laís Bhering Martins,1,2 Adaliene V.M. Ferreira,2 and Karine Clément1,3 1Nutrition and Obesities: Systemic Approaches (NutriOmics, UMRS U1269), INSERM, Sorbonne Université, Paris, France. 2Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 3Nutrition Department, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France. Obesity originates from an imbalance between caloric intake and energy expenditure that promotes adipose tissue expansion, which is necessary to buffer nutrient excess.