{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:44:21Z","timestamp":1786977861581,"version":"build-2736575974"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    Tissue engineering with scaffolds to form transplantable organs is of wide interest. Decellularized tissues have been tested for this purpose, although supplies of healthy donor tissues, vascular recellularization for perfusion, and tissue homeostasis in engineered organs pose challenges. We hypothesized that decellularized human placenta will be suitable for tissue engineering. The universal availability and unique structures of placenta for accommodating tissue, including presence of embedded vessels, were major attractions. We found decellularized placental vessels were reendothelialized by adjacent native cells and bridged vessel defects in rats. In addition, implantation of liver fragments containing all cell types successfully hepatized placenta with maintenance of albumin and urea synthesis, as well as hepatobiliary transport of\n                    <jats:sup>99m<\/jats:sup>\n                    Tc\u2010mebrofenin, up to 3 days in vitro. After hepatized placenta containing autologous liver was transplanted into sheep, tissue units were well\u2010perfused and self\u2010assembled. Histological examination indicated transplanted tissue retained hepatic cord structures with characteristic hepatic organelles, such as gap junctions, and hepatic sinusoids lined by endothelial cells, Kupffer cells, and other cell types. Hepatocytes in this neo\u2010organ expressed albumin and contained glycogen. Moreover, transplantation of hepatized placenta containing autologous tissue rescued sheep in extended partial hepatectomy\u2010induced acute liver failure. This rescue concerned amelioration of injury and induction of regeneration in native liver. The grafted hepatized placenta was intact with healthy tissue that neither proliferated nor was otherwise altered.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    The unique anatomic structure and matrix of human placenta were effective for hepatic tissue engineering. This will advance applications ranging from biological studies, drug development, and toxicology to patient therapies. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:1956\u20101969).\n                  <\/jats:p>","DOI":"10.1002\/hep.29713","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T15:32:46Z","timestamp":1512574366000},"page":"1956-1969","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure"],"prefix":"10.1097","volume":"67","author":[{"given":"Zurab","family":"Kakabadze","sequence":"first","affiliation":[{"name":"Department of Clinical Anatomy,Tbilisi State Medical University,Tbilisi,Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Kakabadze","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy,Tbilisi State Medical University,Tbilisi,Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chakhunashvili","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy,Tbilisi State Medical University,Tbilisi,Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Karalashvili","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy,Tbilisi State Medical University,Tbilisi,Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterine","family":"Berishvili","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy,Tbilisi State Medical University,Tbilisi,Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogeshwar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine,Albert Einstein College of Medicine,Bronx,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine,Albert Einstein College of Medicine,Bronx,NY"},{"name":"Department of Pathology,Albert Einstein College of Medicine,Bronx,NY"},{"name":"Marion Bessin Liver Research Center,Albert Einstein College of Medicine,Bronx,NY"},{"name":"Diabetes Center,Albert Einstein College of Medicine,Bronx,NY"},{"name":"The Irwin S. and Sylvia Chanin Institute for Cancer Research,Albert Einstein College of Medicine,Bronx,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"key":"hep29713-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s40778-017-0075-7","article-title":"Bioengineering hearts: simple yet complex","volume":"3","year":"2017","journal-title":"Curr Stem Cell Rep"},{"key":"hep29713-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.1016\/j.jhep.2015.02.040","article-title":"Cell therapy in liver disease: from liver transplantation to cell factory","volume":"62","year":"2015","journal-title":"J Hepatol"},{"key":"hep29713-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jhep.2016.11.017","article-title":"Role of the inflammasome in acetaminophen\u2010induced liver injury and acute liver failure","volume":"66","year":"2017","journal-title":"J Hepatol"},{"key":"hep29713-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nm.2170","article-title":"Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix","volume":"16","year":"2010","journal-title":"Nat Med"},{"key":"hep29713-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"13079","DOI":"10.1038\/srep13079","article-title":"Decellularized human liver as a natural 3D\u2010scaffold for liver bioengineering and transplantation","volume":"5","year":"2015","journal-title":"Sci Rep"},{"key":"hep29713-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1074\/jbc.274.4.2157","article-title":"Position\u2010specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state","volume":"274","year":"1999","journal-title":"J Biol Chem"},{"key":"hep29713-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ajpath.2010.11.001","article-title":"Perturbations in ataxia telangiectasia mutant signaling pathways after drug\u2010induced acute liver failure and their reversal during rescue of animals by cell therapy","volume":"178","year":"2011","journal-title":"Am J Pathol"},{"key":"hep29713-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-cellbio-100814-125620","article-title":"Placenta: the forgotten organ","volume":"31","year":"2015","journal-title":"Annu Rev Cell Dev Biol"},{"key":"hep29713-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nm1057","article-title":"Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions","volume":"10","year":"2004","journal-title":"Nat Med"},{"key":"hep29713-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0002-9440(10)65675-1","article-title":"Mouse model of venous bypass graft arteriosclerosis","volume":"153","year":"1998","journal-title":"Am J Pathol"},{"key":"hep29713-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s12072-007-9023-4","article-title":"Stage\u2010specific regulation of adhesion molecule expression segregates epithelial stem\/progenitor cells in fetal and adult human livers","volume":"2","year":"2008","journal-title":"Hepatol Int"},{"key":"hep29713-bib-0013-20241017","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1073\/pnas.78.9.5699","article-title":"Lysosomal compartment of macrophages: extending the definition of GERL","volume":"78","year":"1981","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep29713-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.2967\/jnumed.109.062448","article-title":"Adenosine triphosphate\u2013binding cassette subfamily C member 2 is the major transporter of the hepatobiliary imaging agent 99mTc\u2010mebrofenin","volume":"50","year":"2009","journal-title":"J Nucl Med"},{"key":"hep29713-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1073\/pnas.92.13.5860","article-title":"Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV\u2010deficient rats","volume":"92","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"hep29713-bib-0016-20241017","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0014-4827(03)00405-1","article-title":"Metal catalyzed oxidation of extracellular matrix components perturbs hepatocyte survival with activation of intracellular signaling pathways","volume":"291","year":"2003","journal-title":"Exp Cell Res"},{"key":"hep29713-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.biomaterials.2014.11.027","article-title":"Bioengineered transplantable porcine livers with re\u2010endothelialized vasculature","volume":"40","year":"2015","journal-title":"Biomaterials"},{"key":"hep29713-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"12951","DOI":"10.1038\/ncomms12951","article-title":"Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs","volume":"7","year":"2016","journal-title":"Nat Commun"},{"key":"hep29713-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1089\/ten.tea.2011.0738","article-title":"Full\u2010thickness skin wound healing using human placenta derived extracellular matrix containing bioactive molecules","volume":"19","year":"2013","journal-title":"Tissue Eng Part A"},{"key":"hep29713-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/hep.27232","article-title":"Etanercept blocks inflammatory responses orchestrated by TNF\u2010\u03b1 to promote transplanted cell engraftment and proliferation in rat liver","volume":"60","year":"2014","journal-title":"Hepatology"},{"key":"hep29713-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1242\/jcs.095372","article-title":"Spontaneous origin from human embryonic stem cells of early developmental stage liver cells displaying conjoint meso\u2010endodermal phenotype with hepatic functions","volume":"125","year":"2012","journal-title":"J Cell Sci"},{"key":"hep29713-bib-0022-20241017","first-page":"935","article-title":"Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice","volume":"118","year":"2008","journal-title":"J Clin Invest"},{"key":"hep29713-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1182\/blood-2011-07-367680","article-title":"Role of bone marrow transplantation for correcting hemophilia A in mice","volume":"119","year":"2012","journal-title":"Blood"},{"key":"hep29713-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1053\/j.seminhematol.2013.03.023","article-title":"Animal models of hemophilia and related bleeding disorders","volume":"50","year":"2013","journal-title":"Semin Hematol"},{"key":"hep29713-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1111\/ajt.12412","article-title":"Correction of diabetes by minimal mass islet transplantation into the small intestinal submucosa","volume":"13","year":"2013","journal-title":"Am J Transplantation"},{"key":"hep29713-bib-0026-20241017","first-page":"1056","article-title":"Paracrine signals regulate human liver organoid maturation from induced pluripotent stem cells","volume":"144","year":"2017","journal-title":"Development"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.29713","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.29713","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.29713","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201805000-00034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T03:50:47Z","timestamp":1751082647000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201805000-00034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,26]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.29713","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,26]]},"assertion":[{"value":"2017-07-13","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-04","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}