DOCSLIB.ORG

Lymphatic Tissue Engineering and Regeneration Laura Alderfer1, Alicia Wei1 and Donny Hanjaya-Putra1,2,3,4,5,6*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lymphatic Tissue Engineering and Regeneration Laura Alderfer1, Alicia Wei1 and Donny Hanjaya-Putra1,2,3,4,5,6* Alderfer et al. Journal of Biological Engineering (2018) 12:32 https://doi.org/10.1186/s13036-018-0122-7 REVIEW Open Access Lymphatic Tissue Engineering and Regeneration Laura Alderfer1, Alicia Wei1 and Donny Hanjaya-Putra1,2,3,4,5,6* Abstract The lymphatic system is a major circulatory system within the body, responsible for the transport of interstitial fluid, waste products, immune cells, and proteins. Compared to other physiological systems, the molecular mechanisms and underlying disease pathology largely remain to be understood which has hindered advancements in therapeutic options for lymphatic disorders. Dysfunction of the lymphatic system is associated with a wide range of disease phenotypes and has also been speculated as a route to rescue healthy phenotypes in areas including cardiovascular disease, metabolic syndrome, and neurological conditions. This review will discuss lymphatic system functions and structure, cell sources for regenerating lymphatic vessels, current approaches for engineering lymphatic vessels, and specific therapeutic areas that would benefit from advances in lymphatic tissue engineering and regeneration. Keywords: Lymphangiogenesis, Tissue Engineering, Disease Modeling, Wound Healing, Lymphedema, Stem Cells, Biomaterials, Interstitial Fluid, Regeneration I. Introduction to the Lymphatic System and its role Interstitial fluid (IF) is a plasma filtrate that is generated Function by transcapillary filtration and is governed by Starling The lymphatic system is nearly ubiquitous in the human forces, the net difference between hydrostatic and body, present in all tissues except the epidermis, cartil- osmotic pressures, at the microcirculatory level [9]. In age, eye lens, cornea, retina, and bone marrow [1, 2]. order to maintain fluid homeostasis, lymph formation in The main functions of the lymphatic system include the initial lymphatic vessels must be balanced by the net fluid homeostasis and interstitial fluid drainage, immune flux of plasma being filtered out [4]. Transport of IF cell surveillance and trafficking, and lipid absorption [1, from the initial capillaries to the collecting vessels is 3–6]. Lymphangiogenesis, the process of forming new facilitated by IF pressure and systemic forces, including lymphatic vessels from pre-existing vessels, not only blood pressure, respiratory motion massage, peristaltic occurs during development but also in adults during movement, and contractility of surrounding skeletal wound healing, inflammatory responses, and the cancer muscle [10–14]. As a result of constantly clearing IF, the microenvironment [1, 7]. lymphatic system is chronically exposed to and stimu- The lymphatic system includes bone marrow and the lated by fluid flow and pressure [5]. thymus, classified as central or primary lymphoid IF is transported via lymph vessels to lymph nodes and organs, as well as lymphatic vessels, lymph nodes, then returned back to the blood circulation. Properties spleen, adenoids, Peyer’s patches, appendix, and lymph- of the lymphatic capillary wall, hydrostatic pressure, and oid tissue, classified as peripheral or secondary lymphoid protein concentrations in the blood and interstitium are organs [8]. Within the cellular microenvironment in tis- determining factors in the formation of IF [4]. Contained sues, the fluid, proteins, solutes, and extracellular matrix within IF are macromolecules, dissolved solutes, viruses, (ECM) are collectively termed the interstitium [4]. bacteria, certain leukocytes, and cell debris [1]. IF facili- tates the transportation of various molecules between * Correspondence: [email protected] local sites and tissues, including nutrients, waste prod- 1 Department of Aerospace and Mechanical Engineering, Bioengineering ucts, signaling molecules, antigens, and cytokines. The Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA 2Department of Chemical and Biomolecular Engineering, University of Notre specific composition of IF depends on pathogenesis, in- Dame, Notre Dame, IN 46656, USA flammatory responses, and the nearby organs or tissues Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Alderfer et al. Journal of Biological Engineering (2018) 12:32 Page 2 of 26 [4]. Under healthy conditions, IF will comprise approxi- the surrounding tissues as well as blood pressure also as- mately 20% of the body’s weight and 2-4 liters of IF will sist in creating this unidirectional propulsion [14, 25]. be returned to the venous vasculature from the lymph- In addition to these general characteristics of the atic system daily [1, 15]. IF volume is constantly main- lymphatic system that can be found throughout the tained by interstitial buffering mechanisms [8], which body, there are also several specialized functions or not- include structural alterations, differences in forces acting able lymphatic features within organ systems. In the case across the capillary wall, and lymph flow [4]. of regulating lipid uptake in the gastric lymphatic sys- tem, lacteals, specialized lymphatic vessels, are posi- tioned in the villi of lumen next to blood capillaries [26]. Structure Endothelial cells, along with keratinocytes, fibroblasts, Despite the lymphatic system being so extensive, the macrophages, and platelets are involved in the wound field of lymphatic research is very young due to lymph- healing process [27]. In the case of inflammation, the atic specific markers being discovered only 20 years ago. gene expression of LECs is altered and leads to the Since the identification of lymphatic specific markers lymphatic network expanding, along with increased fluid and isolation of lymphatic endothelial cells, key differ- drainage both to and from the site of inflammation [28]. ences between the vascular and lymphatic systems have LVs also contribute to the inflammatory response by been identified, allowing for specific research efforts into draining cytokines and chemokines [26]. The heart con- the lymphatic system without results being confounded tains an extensive lymphatic network, and combined by the inclusion of the vascular system [4]. with the role of the lymphatic system in inflammation, Several key differences exist between blood vessels and targeting lymphangiogenesis in the heart after myocar- lymphatic vessels. Composed of blood endothelial cells dial infarctions to improve recovery has become an area (BECs), blood vessels exhibit tight junctions and a con- of interest [29, 30]. tinuous basal lamina. Conversely, lymphatic vessel (LVs), composed of a single layer of lymphatic endothelial cells II. Complications Associated with the Lymphatic (LECs), have a discontinuous basal lamina as a result of System overlapping and interdigitated endothelial cells [4, 16], Complications associated with the lymphatic system blind ended sacs [16], and a wide lumen [2]. Addition- span a wide spectrum, including congenital disorders, ally, lymphatic capillaries lack pericytes, smooth muscle cancer and side-effects of cancer treatments, cardiovas- cells (SMCs), and mural cell coverage [3, 17]. The ECM cular disease, diabetes, and parasitic infections [25, 31]. and lymphatic capillaries are connected with anchoring While some lymphatic disorders are genetically related, filaments and when the interstitial volume increases, lymphatic complications most often arise as a secondary these anchoring filaments are pulled apart which causes complication following cancer, cardiovascular disease, lymphatic valves to open [18, 19]. These anchoring and immunological diseases [32]. Specific pathologies filaments are composed of collagen VII [20, 21], trans- and areas that could benefit from improved lymphatic membrane integrins, and focal adhesion kinase [17]. function or engineered lymphatic tissue are summarized VE-cadherin joins discontinuous and overlapping endo- in Fig. 1. thelial cells together into buttonlike patterns [22, 23] which are postulated to serve as one-way flaps that fa- Lymphedema cilitate the absorption of cells, fluid, and proteins [4]. IF Lymphedema, characterized by chronic swelling of an enters LVs through these button-like junctions and is fa- extremity, results from local accumulation of interstitial cilitated by the pressure gradient [22]. fluid due to insufficient lymph drainage [4]andisone Unlike the circulatory system, the lymphatic system is of the most prevalent lymphatic-dysfunction conditions a one-way drainage system that originates in tissues and [24]. Globally, up to 250 million people are affected by organs, is funneled through a series of many small ves- lymphedema with the most prevalent cause being the sels emptying into fewer larger vessels, and empties into parasitic disease filariasis [33]. In developed countries, the circulatory system [5]. Continuous fluid flow the most common cause of lymphedema is disruption between blood capillaries and tissues is achieved by of lymphatic pathways, typically from
Load more

Recommended publications
  • Te2, Part Iii
    TERMINOLOGIA EMBRYOLOGICA Second Edition International Embryological Terminology FIPAT The Federative International Programme for Anatomical Terminology A programme of the International Federation of Associations of Anatomists (IFAA) TE2, PART III Contents Caput V: Organogenesis Chapter 5: Organogenesis (continued) Systema respiratorium Respiratory system Systema urinarium Urinary system Systemata genitalia Genital systems Coeloma Coelom Glandulae endocrinae Endocrine glands Systema cardiovasculare Cardiovascular system Systema lymphoideum Lymphoid system Bibliographic Reference Citation: FIPAT. Terminologia Embryologica. 2nd ed. FIPAT.library.dal.ca. Federative International Programme for Anatomical Terminology, February 2017 Published pending approval by the General Assembly at the next Congress of IFAA (2019) Creative Commons License: The publication of Terminologia Embryologica is under a Creative Commons Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) license The individual terms in this terminology are within the public domain. Statements about terms being part of this international standard terminology should use the above bibliographic reference to cite this terminology. The unaltered PDF files of this terminology may be freely copied and distributed by users. IFAA member societies are authorized to publish translations of this terminology. Authors of other works that might be considered derivative should write to the Chair of FIPAT for permission to publish a derivative work. Caput V: ORGANOGENESIS Chapter 5: ORGANOGENESIS
    [Show full text]
  • 29 Assessing the Cardiovascular and Lymphatic Systems
    29 Assessing the Cardiovascular and Lymphatic Systems LEARNING OUTCOMES 1. Describe the anatomy, physiology, and functions of the 5. Explain techniques used to assess cardiovascular and cardiovascular and lymphatic systems. lymphatic structure and function. 2. Describe normal variations in cardiovascular assessment 6. Identify manifestations of impaired cardiovascular structure findings for the older adult. and functions. 3. Give examples of genetic disorders of the cardiovascular system. 4. Identify specific topics for consideration during a health history assessment interview of the patient with cardiovascu- lar or lymphatic disorders. CLINICAL COMPETENCIES 1. Complete a health history for patients having alterations in 3. Assess an ECG strip and identify normal rhythm and cardiac the structure and functions of the cardiovascular or lymphatic events and abnormal cardiac rhythm. systems. 4. Monitor the results of diagnostic tests and communicate 2. Conduct and document a physical assessment of cardiovas- abnormal findings within the interprofessional team. cular and lymphatic status. MAJOR CHAPTER CONCEPTS • Correct structure and function of the cardiovascular and • Manifestations of dysfunction, injury, and disorders affecting lymphatic systems are vital to the transport of oxygen and the cardiovascular and lymphatic systems may be detected carbon dioxide throughout the body and for the return of during a general health assessment as well as during focused excess tissue fluids back to the bloodstream. cardiovascular and lymphatic system
    [Show full text]
  • Molecular Signatures of Tissue-Specific
    Developmental Cell Resource Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration Daniel J. Nolan,1,6 Michael Ginsberg,1,6 Edo Israely,1 Brisa Palikuqi,1 Michael G. Poulos,1 Daylon James,1 Bi-Sen Ding,1 William Schachterle,1 Ying Liu,1 Zev Rosenwaks,2 Jason M. Butler,1 Jenny Xiang,4 Arash Rafii,1,7 Koji Shido,1 Sina Y. Rabbany,1,8 Olivier Elemento,3 and Shahin Rafii1,5,* 1Department of Genetic Medicine, Howard Hughes Medical Institute 2Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine 3HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine 4Genomics Resource Core Facility Weill Cornell Medical College, New York, NY 10065, USA 5Ansary Stem Cell Institute, New York, NY 10065, USA 6Angiocrine Bioscience, New York, NY 10065, USA 7Weill Cornell Medical College-Qatar, Stem Cell and Microenvironment Laboratory, Education City, Qatar Foundation, Doha 24144, Qatar 8Bioengineering Program, Hofstra University, Hempstead, NY 11549, USA *Correspondence: srafi[email protected] http://dx.doi.org/10.1016/j.devcel.2013.06.017 SUMMARY been appreciated. Capillary ECs of the blood brain barrier (BBB) form a restrictive environment for passage between the Microvascular endothelial cells (ECs) within different brain tissue and the circulating blood. Many of the trafficking pro- tissues are endowed with distinct but as yet unrecog- cesses that are passive in other vascular beds are tightly nized structural, phenotypic, and functional attri- controlled in the brain (Rubin and Staddon, 1999). As opposed butes. We devised EC purification, cultivation, to the BBB, the capillary ECs of the kidney glomeruli are fenes- profiling, and transplantation models that establish trated for the filtration of the blood (Churg and Grishman, tissue-specific molecular libraries of ECs devoid of 1975).
    [Show full text]
  • Visualizing B Cell Development: Creating an Immunology Video Game
    VISUALIZING B CELL DEVELOPMENT: CREATING AN IMMUNOLOGY VIDEO GAME By Emily Lunhui Ling A thesis submitted to Johns Hopkins University in conformity with the requirements for the degree of Master of Arts Baltimore, Maryland March, 2016 © 2016 Emily L. Ling All Rights Reserved ABSTRACT e foundational immunology concepts of lymphocyte development are important for beginning science students to comprehend. Video games oer the potential for a novel approach to teaching this complex subject matter by more eectively engaging students in this material. However, currently available educational video games intended to teach immunology have distinct limitations such as a lack of explicit demonstrations of the stages of lymphocyte development and clonal selection. is project identies the content focus and gameplay mechanics of currently available immunology video games. Using this as a basis, a novel approach for developing an immunology video game was outlined with the primary goal of improving integration of educational content. A proof of concept was developed for the B lymphocyte development portion of the game content and a partial prototype was developed in Unity 5 3D. e important contribution of this thesis was the development of a new approach to designing a more eective educational video game specically for immunology. Outcomes of this research will serve to inform future biomedical communicators on how to develop content for active learning games in immunology and provide a guide for designing full length educational video games featuring novel gameplay mechanics such as those identied through this project. Emily L. Ling ii CHAIRPERSONS OF THE SUPERVISORY COMMITTEE esis Preceptor Mark J. Soloski, Ph.D., Professor of Medicine Departments of Medicine, Pathology, Molecular Biology and Genetics, and Molecular Microbiology and Immunology Director, Immunology Training Program e Johns Hopkins University School of Medicine Departmental Advisor David A.
    [Show full text]
  • The Evolving Cardiac Lymphatic Vasculature in Development, Repair and Regeneration
    REVIEWS The evolving cardiac lymphatic vasculature in development, repair and regeneration Konstantinos Klaourakis 1,2, Joaquim M. Vieira 1,2,3 ✉ and Paul R. Riley 1,2,3 ✉ Abstract | The lymphatic vasculature has an essential role in maintaining normal fluid balance in tissues and modulating the inflammatory response to injury or pathogens. Disruption of normal development or function of lymphatic vessels can have severe consequences. In the heart, reduced lymphatic function can lead to myocardial oedema and persistent inflammation. Macrophages, which are phagocytic cells of the innate immune system, contribute to cardiac development and to fibrotic repair and regeneration of cardiac tissue after myocardial infarction. In this Review, we discuss the cardiac lymphatic vasculature with a focus on developments over the past 5 years arising from the study of mammalian and zebrafish model organisms. In addition, we examine the interplay between the cardiac lymphatics and macrophages during fibrotic repair and regeneration after myocardial infarction. Finally, we discuss the therapeutic potential of targeting the cardiac lymphatic network to regulate immune cell content and alleviate inflammation in patients with ischaemic heart disease. The circulatory system of vertebrates is composed of two after MI. In this Review, we summarize the current complementary vasculatures, the blood and lymphatic knowledge on the development, structure and function vascular systems1. The blood vasculature is a closed sys- of the cardiac lymphatic vasculature, with an emphasis tem responsible for transporting gases, fluids, nutrients, on breakthroughs over the past 5 years in the study of metabolites and cells to the tissues2. This extravasation of cardiac lymphatic heterogeneity in mice and zebrafish.
    [Show full text]
  • Review Article Mesenchymal Stromal Cells Affect Disease Outcomes Via Macrophage Polarization
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Crossref Hindawi Publishing Corporation Stem Cells International Volume 2015, Article ID 989473, 11 pages http://dx.doi.org/10.1155/2015/989473 Review Article Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization Guoping Zheng,1 Menghua Ge,1 Guanguan Qiu,1 Qiang Shu,2 and Jianguo Xu1,3 1 Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China 2The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China 3The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China Correspondence should be addressed to Jianguo Xu; [email protected] Received 18 May 2015; Accepted 30 June 2015 Academic Editor: Armand Keating Copyright © 2015 Guoping Zheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor- stimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response.
    [Show full text]
  • Are You Ready for ICD-10-PCS? Expert Tips, Tools, and Guidance to Make the Transition Simple
    Are You Ready for ICD-10-PCS? Expert Tips, Tools, and Guidance to Make the Transition Simple By Amy Crenshaw Pritchett February 19, 2014 1 Agenda In this webinar: Expand your understanding of ICD-10-PCS with can’t miss ICD-10-PCS coding conventions & guidelines. Understand the basic differences between ICD-9-CM Volume 3 and ICD-10-PCS. Learn code structure, organization, & characters: Step 1 to coding section “0” ICD-10-PCS? Pinpoint the body system. To build your ICD-10-PCS code, you must identify the root operation. Study 7 options when assigning your PCS code’s 5th character. Master how to determine the device value for your PCS code’s character. Raise your awareness of unique ICD-10-PCS challenges pertaining to documentation and specificity: Prepare physicians now for more detailed transfusion notes under ICD- 10-PCS. Discover why writing “Right Carotid Endarterectomy” won’t be enough. Know where to find ICD-10-PCS tools, techniques, and best practices. 2 Understanding ICD-10-PCS ICD-10-PCS is a major departure from ICD-9-CM procedure coding, requiring you to know which root word applies. Effective October 1, 2014, this procedure coding system will be used to collect data, determine payment, and support the electronic health record for all inpatient procedures performed in the US. 3 Gear Up for ICD-10-PCS This procedure coding system is starkly different from ICD-9-CM procedure coding: Every ICD-10-PCS code has seven characters, each character defining one aspect of the procedure performed. For instance, not correctly identifying your physician’s approach – the fifth character – and not being able to distinguish between similar root operations can throw off your claims accuracy! 4 Converting to ICD-10-PCS Have your inpatient coders and clinical documentation specialists begun preparing for ICD-10-PCS yet? That’s why we’re here today … to ease your transition from ICD-9-CM procedure coding to ICD-10-PCS.
    [Show full text]
  • Overview of Gastrointestinal Function
    Overview of Gastrointestinal Function George N. DeMartino, Ph.D. Department of Physiology University of Texas Southwestern Medical Center Dallas, TX 75390 The gastrointestinal system Functions of the gastrointestinal system • Digestion • Absorption • Secretion • Motility • Immune surveillance and tolerance GI-OP-13 Histology of the GI tract Blood or Lumenal Serosal Side or Mucosal Side Structure of a villus Villus Lamina propria Movement of substances across the epithelial layer Tight junctions X Lumen Blood Apical membrane Basolateral membrane X X transcellular X X paracellular GI-OP-19 Histology of the GI tract Blood or Lumenal Serosal Side or Mucosal Side Motility in the gastrointestinal system Propulsion net movement by peristalsis Mixing for digestion and absorption Separation sphincters Storage decreased pressure GI-OP-42 Intercellular signaling in the gastrointestinal system • Neural • Hormonal • Paracrine GI-OP-10 Neural control of the GI system • Extrinsic nervous system autonomic central nervous system • Intrinsic (enteric) nervous system entirely with the GI system GI-OP-14 The extrinsic nervous system The intrinsic nervous system forms complete functional circuits Sensory neurons Interneurons Motor neurons (excitatory and inhibitory) Parasympathetic nerves regulate functions of the intrinsic nervous system Y Reflex control of gastrointestinal functions Vago-vagal Afferent reflex Salivary Glands Composition of Saliva O Proteins α−amylase lactoferrin lipase RNase lysozyme et al mucus O Electrolyte solution water Na+ , K + - HCO3
    [Show full text]
  • Type 3 Innate Lymphoid Cells a Stromal Cell Niche for Human and Mouse
    A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells Kerim Hoorweg, Priyanka Narang, Zhi Li, Anne Thuery, Natalie Papazian, David R. Withers, Mark C. Coles and Tom This information is current as Cupedo of September 28, 2021. J Immunol 2015; 195:4257-4263; Prepublished online 16 September 2015; doi: 10.4049/jimmunol.1402584 http://www.jimmunol.org/content/195/9/4257 Downloaded from References This article cites 42 articles, 9 of which you can access for free at: http://www.jimmunol.org/content/195/9/4257.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 28, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells Kerim Hoorweg,*,1 Priyanka Narang,†,1 Zhi Li,† Anne Thuery,† Natalie Papazian,* David R.
    [Show full text]
  • Lymphangiogenesis and Angiogenesis During Human Fetal
    Roost et al. Vascular Cell 2014, 6:22 http://www.vascularcell.com/content/6/1/22 VASCULAR CELL RESEARCH Open Access Lymphangiogenesis and angiogenesis during human fetal pancreas development Matthias S Roost1, Liesbeth van Iperen1, Ana de Melo Bernardo1, Christine L Mummery1, Françoise Carlotti2, Eelco JP de Koning2,3 and Susana M Chuva de Sousa Lopes1,4* Abstract Background: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies. Methods: We examined angiogenesis and lymphangiogenesis during human pancreas development between 9 and 22 weeks of gestation (W9-W22) by immunohistochemistry. Results: As early as W9, the peri-pancreatic mesenchyme was populated by CD31-expressing blood vessels as well as LYVE1- and PDPN-expressing lymphatic vessels. The appearance of smooth muscle cell-coated blood vessels in the intra-pancreatic mesenchyme occurred only several weeks later and from W14.5 onwards the islets of Langerhans also became heavily irrigated by blood vessels. In contrast to blood vessels, LYVE1- and PDPN-expressing lymphatic vessels were restricted to the peri-pancreatic mesenchyme until later in development (W14.5-W17), and some of these invading lymphatic vessels contained smooth muscle cells at W17.
    [Show full text]
  • Sporadic (Nonhereditary) Colorectal Cancer: Introduction
    Sporadic (Nonhereditary) Colorectal Cancer: Introduction Colorectal cancer affects about 5% of the population, with up to 150,000 new cases per year in the United States alone. Cancer of the large intestine accounts for 21% of all cancers in the US, ranking second only to lung cancer in mortality in both males and females. It is, however, one of the most potentially curable of gastrointestinal cancers. Colorectal cancer is detected through screening procedures or when the patient presents with symptoms. Screening is vital to prevention and should be a part of routine care for adults over the age of 50 who are at average risk. High-risk individuals (those with previous colon cancer , family history of colon cancer , inflammatory bowel disease, or history of colorectal polyps) require careful follow-up. There is great variability in the worldwide incidence and mortality rates. Industrialized nations appear to have the greatest risk while most developing nations have lower rates. Unfortunately, this incidence is on the increase. North America, Western Europe, Australia and New Zealand have high rates for colorectal neoplasms (Figure 2). Figure 1. Location of the colon in the body. Figure 2. Geographic distribution of sporadic colon cancer . Symptoms Colorectal cancer does not usually produce symptoms early in the disease process. Symptoms are dependent upon the site of the primary tumor. Cancers of the proximal colon tend to grow larger than those of the left colon and rectum before they produce symptoms. Abnormal vasculature and trauma from the fecal stream may result in bleeding as the tumor expands in the intestinal lumen.
    [Show full text]
  • GLOSSARY of MEDICAL and ANATOMICAL TERMS
    GLOSSARY of MEDICAL and ANATOMICAL TERMS Abbreviations: • A. Arabic • abb. = abbreviation • c. circa = about • F. French • adj. adjective • G. Greek • Ge. German • cf. compare • L. Latin • dim. = diminutive • OF. Old French • ( ) plural form in brackets A-band abb. of anisotropic band G. anisos = unequal + tropos = turning; meaning having not equal properties in every direction; transverse bands in living skeletal muscle which rotate the plane of polarised light, cf. I-band. Abbé, Ernst. 1840-1905. German physicist; mathematical analysis of optics as a basis for constructing better microscopes; devised oil immersion lens; Abbé condenser. absorption L. absorbere = to suck up. acervulus L. = sand, gritty; brain sand (cf. psammoma body). acetylcholine an ester of choline found in many tissue, synapses & neuromuscular junctions, where it is a neural transmitter. acetylcholinesterase enzyme at motor end-plate responsible for rapid destruction of acetylcholine, a neurotransmitter. acidophilic adj. L. acidus = sour + G. philein = to love; affinity for an acidic dye, such as eosin staining cytoplasmic proteins. acinus (-i) L. = a juicy berry, a grape; applied to small, rounded terminal secretory units of compound exocrine glands that have a small lumen (adj. acinar). acrosome G. akron = extremity + soma = body; head of spermatozoon. actin polymer protein filament found in the intracellular cytoskeleton, particularly in the thin (I-) bands of striated muscle. adenohypophysis G. ade = an acorn + hypophyses = an undergrowth; anterior lobe of hypophysis (cf. pituitary). adenoid G. " + -oeides = in form of; in the form of a gland, glandular; the pharyngeal tonsil. adipocyte L. adeps = fat (of an animal) + G. kytos = a container; cells responsible for storage and metabolism of lipids, found in white fat and brown fat.
    [Show full text]