{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:48:00Z","timestamp":1778644080368,"version":"3.51.4"},"reference-count":12,"publisher":"Proceedings of the National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,6,8]]},"abstract":"<jats:p>\n                    Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl\n                    <jats:sub>4<\/jats:sub>\n                    , a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named \u201chepatocyte-sinusoid alignment\u201d (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0909374107","type":"journal-article","created":{"date-parts":[[2010,5,19]],"date-time":"2010-05-19T22:59:53Z","timestamp":1274309993000},"page":"10371-10376","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":295,"title":["Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration"],"prefix":"10.1073","volume":"107","author":[{"given":"Stefan","family":"Hoehme","sequence":"first","affiliation":[{"name":"Interdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, H\u00e4rtelstrasse 16-18, D-04107 Leipzig, Germany;"}]},{"given":"Marc","family":"Brulport","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Alexander","family":"Bauer","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Essam","family":"Bedawy","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Wiebke","family":"Schormann","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Matthias","family":"Hermes","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Verena","family":"Puppe","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Rolf","family":"Gebhardt","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany;"}]},{"given":"Sebastian","family":"Zellmer","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany;"}]},{"given":"Michael","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of T\u00fcbingen, Wilhelmstrasse 56, 72074 T\u00fcbingen, Germany;"}]},{"given":"Ernesto","family":"Bockamp","sequence":"additional","affiliation":[{"name":"Clinical School of the Johannes Gutenberg\u2013University Mainz Institute for Toxicology, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; and"}]},{"given":"Tobias","family":"Timmel","sequence":"additional","affiliation":[{"name":"Biofluidmechanics Laboratory, Charite\u2013Universit\u00e4tsmedizin Berlin, Berlin, Germany"}]},{"given":"Jan G.","family":"Hengstler","sequence":"additional","affiliation":[{"name":"Leibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;"}]},{"given":"Dirk","family":"Drasdo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, H\u00e4rtelstrasse 16-18, D-04107 Leipzig, Germany;"},{"name":"Institut National de Recherche en Informatique et en Automatique (INRIA), Unit Rocquencourt B.P. 105, 78153, Le Chesnay Cedex, France;"}]}],"member":"341","published-online":{"date-parts":[[2010,5,19]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.60"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-527"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0748233706070982"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2007.01.010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.94.028102"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10955-007-9289-x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1715"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608660104"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079562"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116451"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2005.12.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1084952102001301"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0909374107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:28:40Z","timestamp":1649788120000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0909374107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,19]]},"references-count":12,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2010,6,8]]}},"alternative-id":["10.1073\/pnas.0909374107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0909374107","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.6934957.7125055","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.6934957.8080057","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,19]]},"assertion":[{"value":"2010-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}