The passive biomechanics of human pelvic collecting lymphatic vessels
Identifieur interne : 009402 ( Ncbi/Merge ); précédent : 009401; suivant : 009403The passive biomechanics of human pelvic collecting lymphatic vessels
Auteurs : Dimitrios Athanasiou [Royaume-Uni] ; Lowell T. Edgar [Royaume-Uni] ; Mohammad Jafarnejad [Royaume-Uni] ; Katherine Nixon [Royaume-Uni] ; Delfim Duarte [Royaume-Uni] ; Edwin D. Hawkins [Australie] ; Samira Jamalian [Royaume-Uni] ; Paula Cunnea [Royaume-Uni] ; Cristina Lo Celso [Royaume-Uni] ; Shunichi Kobayashi [Japon] ; Christina Fotopoulou [Royaume-Uni] ; James E. Moore [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Abstract
The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.
Url:
DOI: 10.1371/journal.pone.0183222
PubMed: 28827843
PubMed Central: 5565099
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Edgar</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Bioengineering, Imperial College, London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Bioengineering, Imperial College, London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Jafarnejad, Mohammad" sort="Jafarnejad, Mohammad" uniqKey="Jafarnejad M" first="Mohammad" last="Jafarnejad">Mohammad Jafarnejad</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Bioengineering, Imperial College, London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Bioengineering, Imperial College, London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Nixon, Katherine" sort="Nixon, Katherine" uniqKey="Nixon K" first="Katherine" last="Nixon">Katherine Nixon</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Duarte, Delfim" sort="Duarte, Delfim" uniqKey="Duarte D" first="Delfim" last="Duarte">Delfim Duarte</name><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Department of Life Sciences and the Francis Crick Institute, Imperial College London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Life Sciences and the Francis Crick Institute, Imperial College London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Hawkins, Edwin D" sort="Hawkins, Edwin D" uniqKey="Hawkins E" first="Edwin D." last="Hawkins">Edwin D. Hawkins</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Immunology Division at the Walter and Eliza Hall, Institute of Medical Research, Department of Medical Biology, University of Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology Division at the Walter and Eliza Hall, Institute of Medical Research, Department of Medical Biology, University of Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Jamalian, Samira" sort="Jamalian, Samira" uniqKey="Jamalian S" first="Samira" last="Jamalian">Samira Jamalian</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Bioengineering, Imperial College, London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Bioengineering, Imperial College, London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Cunnea, Paula" sort="Cunnea, Paula" uniqKey="Cunnea P" first="Paula" last="Cunnea">Paula Cunnea</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Lo Celso, Cristina" sort="Lo Celso, Cristina" uniqKey="Lo Celso C" first="Cristina" last="Lo Celso">Cristina Lo Celso</name><affiliation wicri:level="3"><nlm:aff id="aff003"><addr-line>Department of Life Sciences and the Francis Crick Institute, Imperial College London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Life Sciences and the Francis Crick Institute, Imperial College London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Kobayashi, Shunichi" sort="Kobayashi, Shunichi" uniqKey="Kobayashi S" first="Shunichi" last="Kobayashi">Shunichi Kobayashi</name><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Department of Mechanical Engineering and Robotics, Shinshu University, Ueda, Nagano, Japan</addr-line></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Mechanical Engineering and Robotics, Shinshu University, Ueda, Nagano</wicri:regionArea><wicri:noRegion>Nagano</wicri:noRegion></affiliation></author><author><name sortKey="Fotopoulou, Christina" sort="Fotopoulou, Christina" uniqKey="Fotopoulou C" first="Christina" last="Fotopoulou">Christina Fotopoulou</name><affiliation wicri:level="3"><nlm:aff id="aff002"><addr-line>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Moore, James E" sort="Moore, James E" uniqKey="Moore J" first="James E." last="Moore">James E. Moore</name><affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>Department of Bioengineering, Imperial College, London, South Kensington Campus, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Bioengineering, Imperial College, London, South Kensington Campus, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gashev, Aa" uniqKey="Gashev A">AA Gashev</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X Deng</name></author><author><name sortKey="Marinov, G" uniqKey="Marinov G">G Marinov</name></author><author><name sortKey="Marois, Y" uniqKey="Marois Y">Y Marois</name></author><author><name sortKey="Guidoin, R" uniqKey="Guidoin R">R Guidoin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahbar, E" uniqKey="Rahbar E">E Rahbar</name></author><author><name sortKey="Weimer, J" uniqKey="Weimer J">J Weimer</name></author><author><name sortKey="Gibbs, H" uniqKey="Gibbs H">H Gibbs</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28827843</article-id><article-id pub-id-type="pmc">5565099</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0183222</article-id><article-id pub-id-type="publisher-id">PONE-D-17-01039</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Elastin</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Collagens</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Physical Sciences</subject><subj-group><subject>Materials Science</subject><subj-group><subject>Material Properties</subject><subj-group><subject>Mechanical Properties</subject><subj-group><subject>Stiffness</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Muscle Physiology</subject><subj-group><subject>Muscle Contraction</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Muscle Physiology</subject><subj-group><subject>Muscle Contraction</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biomechanics</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Behavior</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Cancer Treatment</subject><subj-group><subject>Surgical Oncology</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Clinical Medicine</subject><subj-group><subject>Clinical Oncology</subject><subj-group><subject>Surgical Oncology</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Clinical Oncology</subject><subj-group><subject>Surgical Oncology</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Oncology</subject><subj-group><subject>Cancers and Neoplasms</subject><subj-group><subject>Gynecological Tumors</subject><subj-group><subject>Ovarian Cancer</subject></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>The passive biomechanics of human pelvic collecting lymphatic vessels</article-title><alt-title alt-title-type="running-head">Biomechanics of human collecting lymphatics</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Athanasiou</surname><given-names>Dimitrios</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Investigation</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8586-1605</contrib-id><name><surname>Edgar</surname><given-names>Lowell T.</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib><contrib contrib-type="author"><name><surname>Jafarnejad</surname><given-names>Mohammad</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nixon</surname><given-names>Katherine</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Duarte</surname><given-names>Delfim</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Visualization</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hawkins</surname><given-names>Edwin D.</given-names></name><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jamalian</surname><given-names>Samira</given-names></name><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cunnea</surname><given-names>Paula</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lo Celso</surname><given-names>Cristina</given-names></name><role content-type="http://credit.casrai.org/">Resources</role><role content-type="http://credit.casrai.org/">Supervision</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kobayashi</surname><given-names>Shunichi</given-names></name><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fotopoulou</surname><given-names>Christina</given-names></name><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moore</surname><given-names>James E.</given-names><suffix>Jr.</suffix></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Project administration</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="author-notes" rid="econtrib001"><sup>‡</sup></xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Department of Bioengineering, Imperial College, London, South Kensington Campus, London, United Kingdom</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Life Sciences and the Francis Crick Institute, Imperial College London, South Kensington Campus, London, United Kingdom</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Immunology Division at the Walter and Eliza Hall, Institute of Medical Research, Department of Medical Biology, University of Melbourne, Victoria, Australia</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Department of Mechanical Engineering and Robotics, Shinshu University, Ueda, Nagano, Japan</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Breslin</surname><given-names>Jerome W.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>USF Health Morsani College of Medicine, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>The authors have declared that no competing interest exist.</p></fn><fn fn-type="other" id="econtrib001"><p>‡ DA and LTE are co-first authorship and CF and JEM are co-senior authorship on this work.</p></fn><corresp id="cor001">* E-mail: <email>l.edgar@imperial.ac.uk</email></corresp></author-notes><pub-date pub-type="epub"><day>21</day><month>8</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>12</volume><issue>8</issue><elocation-id>e0183222</elocation-id><history><date date-type="received"><day>9</day><month>1</month><year>2017</year></date><date date-type="accepted"><day>1</day><month>8</month><year>2017</year></date></history><permissions><copyright-statement>© 2017 Athanasiou et al</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>Athanasiou et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="pone.0183222.pdf"></self-uri><abstract><p>The lymphatic system has a major significance in the metastatic pathways in women’s cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.</p></abstract><funding-group><award-group id="award001"><funding-source><institution>Foundation for the National Institutes of Health (US)</institution></funding-source><award-id>U01-HL-123420</award-id><principal-award-recipient><name><surname>Moore</surname><given-names>James E.</given-names><suffix>Jr</suffix></name></principal-award-recipient></award-group><funding-statement>The authors gratefully acknowledge the following sources of support: The Royal Society, The Royal Academy of Engineering, The Sir Leon Bagrit Trust, the United States National Institutes of Health (NIH) Grant U01-HL-123420, the GABBA PhD program (FCT fellowship SFRH/BD/52195/2013), and the Ovarian Cancer Action and Sainsbury’s Imperial Private Healthcare Scholarship. This research was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The authors gratefully acknowledge the assistance of Imperial College Experimental Cancer Medicine Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="4"></fig-count><table-count count="1"></table-count><page-count count="12"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All data are within the paper and Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All data are within the paper and Supporting Information files.</p></notes></front></pmc><affiliations><list><country><li>Australie</li><li>Japon</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Athanasiou, Dimitrios" sort="Athanasiou, Dimitrios" uniqKey="Athanasiou D" first="Dimitrios" last="Athanasiou">Dimitrios Athanasiou</name></region><name sortKey="Cunnea, Paula" sort="Cunnea, Paula" uniqKey="Cunnea P" first="Paula" last="Cunnea">Paula Cunnea</name><name sortKey="Duarte, Delfim" sort="Duarte, Delfim" uniqKey="Duarte D" first="Delfim" last="Duarte">Delfim Duarte</name><name sortKey="Edgar, Lowell T" sort="Edgar, Lowell T" uniqKey="Edgar L" first="Lowell T." last="Edgar">Lowell T. Edgar</name><name sortKey="Fotopoulou, Christina" sort="Fotopoulou, Christina" uniqKey="Fotopoulou C" first="Christina" last="Fotopoulou">Christina Fotopoulou</name><name sortKey="Jafarnejad, Mohammad" sort="Jafarnejad, Mohammad" uniqKey="Jafarnejad M" first="Mohammad" last="Jafarnejad">Mohammad Jafarnejad</name><name sortKey="Jamalian, Samira" sort="Jamalian, Samira" uniqKey="Jamalian S" first="Samira" last="Jamalian">Samira Jamalian</name><name sortKey="Lo Celso, Cristina" sort="Lo Celso, Cristina" uniqKey="Lo Celso C" first="Cristina" last="Lo Celso">Cristina Lo Celso</name><name sortKey="Moore, James E" sort="Moore, James E" uniqKey="Moore J" first="James E." last="Moore">James E. Moore</name><name sortKey="Nixon, Katherine" sort="Nixon, Katherine" uniqKey="Nixon K" first="Katherine" last="Nixon">Katherine Nixon</name></country><country name="Australie"><noRegion><name sortKey="Hawkins, Edwin D" sort="Hawkins, Edwin D" uniqKey="Hawkins E" first="Edwin D." last="Hawkins">Edwin D. Hawkins</name></noRegion></country><country name="Japon"><noRegion><name sortKey="Kobayashi, Shunichi" sort="Kobayashi, Shunichi" uniqKey="Kobayashi S" first="Shunichi" last="Kobayashi">Shunichi Kobayashi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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