{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:13:20Z","timestamp":1775816000793,"version":"3.50.1"},"reference-count":42,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2016,1,14]]},"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7\u2005days post-op.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gutjnl-2015-310409","type":"journal-article","created":{"date-parts":[[2016,2,14]],"date-time":"2016-02-14T20:09:19Z","timestamp":1455480559000},"page":"1297-1305","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment"],"prefix":"10.1136","volume":"66","author":[{"given":"Pedro","family":"Melgar-Lesmes","sequence":"first","affiliation":[{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Balcells","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"},{"name":"Bioengineering Department, Institut Qu\u00edmic de Sarri\u00e0, Ramon Llull Univ, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elazer R","family":"Edelman","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"},{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2016,2,5]]},"reference":[{"key":"2025090711033453000_66.7.1297.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2008.07.007"},{"key":"2025090711033453000_66.7.1297.2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrgastro.2012.225","article-title":"Ischaemia-reperfusion injury in liver transplantation\u2014from bench to bedside","volume":"10","author":"Zhai","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2025090711033453000_66.7.1297.3","unstructured":"US Department of Health and Human Services. Organ Procurement and Transplantation Network. 2014. http:\/\/optn.transplant.hrsa.gov\/data\/"},{"key":"2025090711033453000_66.7.1297.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12271"},{"key":"2025090711033453000_66.7.1297.5","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23354"},{"key":"2025090711033453000_66.7.1297.6","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0437"},{"key":"2025090711033453000_66.7.1297.7","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23608"},{"key":"2025090711033453000_66.7.1297.8","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20411"},{"key":"2025090711033453000_66.7.1297.9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2119\/2007-00134.Vardanian","article-title":"Molecular mediators of liver ischemia and reperfusion injury: a brief review","volume":"14","author":"Vardanian","year":"2008","journal-title":"Mol Med"},{"key":"2025090711033453000_66.7.1297.10","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.9323"},{"key":"2025090711033453000_66.7.1297.11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2507"},{"key":"2025090711033453000_66.7.1297.12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070247"},{"key":"2025090711033453000_66.7.1297.13","doi-asserted-by":"publisher","DOI":"10.1038\/nature09493"},{"key":"2025090711033453000_66.7.1297.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063889"},{"key":"2025090711033453000_66.7.1297.15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66025"},{"key":"2025090711033453000_66.7.1297.16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20434"},{"key":"2025090711033453000_66.7.1297.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.06.017"},{"key":"2025090711033453000_66.7.1297.18","first-page":"935","article-title":"Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice","volume":"118","author":"Follenzi","year":"2008","journal-title":"J Clin Invest"},{"key":"2025090711033453000_66.7.1297.19","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21845"},{"key":"2025090711033453000_66.7.1297.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2007.12.005"},{"key":"2025090711033453000_66.7.1297.21","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7051com"},{"key":"2025090711033453000_66.7.1297.22","doi-asserted-by":"crossref","first-page":"I233","DOI":"10.1161\/CIRCULATIONAHA.105.000687","article-title":"Cell-matrix contact prevents recognition and damage of endothelial cells in states of heightened immunity","volume":"114","author":"Methe","year":"2006","journal-title":"Circulation"},{"key":"2025090711033453000_66.7.1297.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2009.11.006"},{"key":"2025090711033453000_66.7.1297.24","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.80"},{"key":"2025090711033453000_66.7.1297.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.05.011"},{"key":"2025090711033453000_66.7.1297.26","unstructured":"Indolfi L , Iaconetti C , Monteforte A , et al . Harnessing cell: materials interactions to develop innovative strategy for the recruitment of progenitor cells. Society for Biomaterials. Annual Meeting; 2014; Abstract 250."},{"key":"2025090711033453000_66.7.1297.27","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26754"},{"key":"2025090711033453000_66.7.1297.28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/TP.0b013e31825774d7","article-title":"Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant","volume":"94","author":"Fondevila","year":"2012","journal-title":"Transplantation"},{"key":"2025090711033453000_66.7.1297.29","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23558"},{"key":"2025090711033453000_66.7.1297.30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101925"},{"key":"2025090711033453000_66.7.1297.31","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2011.53"},{"key":"2025090711033453000_66.7.1297.32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116451"},{"key":"2025090711033453000_66.7.1297.33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58789"},{"key":"2025090711033453000_66.7.1297.34","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2604rev"},{"key":"2025090711033453000_66.7.1297.35","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.05.009"},{"key":"2025090711033453000_66.7.1297.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.02.012"},{"key":"2025090711033453000_66.7.1297.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.06.052"},{"key":"2025090711033453000_66.7.1297.38","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.66"},{"key":"2025090711033453000_66.7.1297.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.042"},{"key":"2025090711033453000_66.7.1297.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2006.10.052"},{"key":"2025090711033453000_66.7.1297.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2007.04.074"},{"key":"2025090711033453000_66.7.1297.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802463105"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gutjnl-2015-310409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T18:03:43Z","timestamp":1757268223000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gutjnl-2015-310409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,5]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,6,6]]},"published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1136\/gutjnl-2015-310409"],"URL":"https:\/\/doi.org\/10.1136\/gutjnl-2015-310409","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,5]]}}}