{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:39:58Z","timestamp":1791405598469,"version":"4.3.3"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5753,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Small, extraportal, hepatic parenchymal cells, positive for biliary-type cytokeratins, may represent hepatic stem cells, canals of Hering (CoH), and\/or ductal plate remnants. We evaluated these cells 3 dimensionally in normal human liver and massive necrosis. Tissues from normal human livers and from 1 liver with acetaminophen-induced massive necrosis were serially sectioned, immunostained for cytokeratin 19 (CK19), and sequentially photographed. Images were examined to determine 3-dimensional relationships among CK19-positive cells. Immunostains for other hepatocyte and progenitor cell markers were examined. In normal livers, intraparenchymal CK19-positive cells lined up as linear arrays in sequential levels. One hundred of 106 (94.3%) defined, complete arrays within levels examined, most having 1 terminus at a bile duct, the other in the lobule, beyond the limiting plate. In massive necrosis, there were 767 individual CK19-positive cells or clusters around a single portal tract, 747 (97.4%) of which were spatially related forming arborizing networks connected to the interlobular bile duct by single tributaries. C-kit was positive in normal CoH. CK19 co-expressed with HepPar1, c-kit, and \u03b1-fetoprotein (AFP) in parenchymal cells in massive necrosis. Small, extraportal, biliary-type parenchymal cells represent cross-sections of the CoH that radiate from the portal tract, usually extending past the limiting plate into the proximate third of the hepatic lobule. The 3-dimensional structure of ductular reactions in massive necrosis suggests that these reactions are proliferations of the cells lining the CoH. Therefore, the CoH consist of, or harbor, facultative hepatic stem cells in humans.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510300614","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:41:30Z","timestamp":1091000490000},"page":"1425-1433","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":589,"title":["The canals of hering and hepatic stem cells in humans"],"prefix":"10.1097","volume":"30","author":[{"given":"Neil D.","family":"Theise","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romil","family":"Saxena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard C.","family":"Portmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swan N.","family":"Thung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Chiriboga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"BIB1","first-page":"105","volume":"7","author":"Sell","year":"1994","journal-title":"Mod Pathol"},{"key":"BIB2","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1093\/carcin\/8.11.1737","volume":"8","author":"Evarts","year":"1987","journal-title":"Carcinogenesis"},{"key":"BIB3","first-page":"329","volume":"24","author":"Yasui","year":"1997","journal-title":"Hepatology"},{"key":"BIB4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0168-8278(98)80065-2","volume":"29","author":"Roskams","year":"1998","journal-title":"J Hepatol"},{"key":"BIB5","first-page":"771","volume":"152","author":"Crosby","year":"1998","journal-title":"Am J Pathol"},{"key":"BIB6","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1002\/hep.1840160604","volume":"16","author":"Hsia","year":"1992","journal-title":"Hepatology"},{"key":"BIB7","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/hep.1840200404","volume":"20","author":"Su","year":"1994","journal-title":"Hepatology"},{"key":"BIB8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1002\/hep.510230312","volume":"23","author":"Haruna","year":"1996","journal-title":"Hepatology"},{"key":"BIB9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/hep.510270202","volume":"27","author":"Sell","year":"1998","journal-title":"Hepatology"},{"key":"BIB10","author":"Gerber","year":"1983","unstructured":"Phenotypic characterization of hepatic proliferation: Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver. Am J Pathol 1983; 110-114."},{"key":"BIB11","first-page":"259","volume":"15","author":"Roskams","year":"1998","journal-title":"Sem Diag Pathol"},{"key":"BIB12","first-page":"407","volume":"114","author":"Thung","year":"1990","journal-title":"Arch Pathol Lab Med"},{"key":"BIB13","first-page":"230a","volume":"22","author":"Park","year":"1995","journal-title":"Hepatology"},{"key":"BIB14","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1365-2559.1988.tb02092.x","volume":"13","author":"Van Eyken","year":"1988","journal-title":"Histopathology"},{"key":"BIB15","first-page":"496","volume":"54","author":"Hering","year":"1865","journal-title":"Math Naturic KL"},{"key":"BIB16","first-page":"105","volume-title":"Morphology of the liver","author":"Elias","year":"1969","unstructured":"Intrahepatic biliary passages. In: eds. Morphology of the liver. New York: Academic Press. 1969; 105-123."},{"key":"BIB17","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0016-5085(19)32475-8","volume":"69","author":"Layden","year":"1975","journal-title":"Gastroenterology"},{"key":"BIB18","first-page":"35","volume-title":"Pathology of the Liver","author":"MacSween","year":"1994","unstructured":"Developmental anatomy and normal structure. In: eds. Pathology of the Liver, Ed. 3. London: Churchill Livingstone. 1994; 35-36."},{"key":"BIB19","first-page":"11","volume-title":"Hepatology. A textbook of liver disease","volume":"1","author":"Jones","year":"1996","unstructured":"Anatomy of the normal liver. In: eds. Hepatology. A textbook of liver disease, Vol. 1, Ed. 3. Philadelphia: W. B. Saunders Co.. 1996; 1:11-12."},{"key":"BIB20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1600-0676.1983.tb00865.x","volume":"3","author":"Baptista","year":"1983","journal-title":"Liver"},{"key":"BIB21","first-page":"112","volume":"18","author":"Landing","year":"1970","journal-title":"Pediatr Univ Tokyo"},{"key":"BIB22","first-page":"480","volume-title":"The Liver","author":"Landing","year":"1973","unstructured":"Diseases of the bile ducts in children. In: eds. The Liver. Baltimore: Williams & Wilkins. 1973; 480-491."},{"key":"BIB23","first-page":"122","volume-title":"Transplantation Pathology - Hepatic Morphogenesis","author":"Landing","year":"1991","unstructured":"Considerations of some architectural properties of the biliary tree and liver in childhood. In: eds. Transplantation Pathology - Hepatic Morphogenesis. Perspect Pediatr Pathol. Basel, Karger 1991; 122-142."},{"key":"BIB24","first-page":"639","volume":"38","author":"Steiner","year":"1961","journal-title":"Am J Pathology"},{"key":"BIB25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/hep.510280206","volume":"28","author":"Crawford","year":"1998","journal-title":"Hepatology"},{"key":"BIB26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/path.1711660407","volume":"166","author":"Koukoulis","year":"1992","journal-title":"J Pathol"},{"key":"BIB27","first-page":"407","volume":"23","author":"Faktor","year":"1992","journal-title":"Ontogenez"},{"key":"BIB28","first-page":"1441","volume":"140","author":"De Vos","year":"1992","journal-title":"Am Pathol"},{"key":"BIB29","first-page":"32s","volume":"23","author":"Roskams","year":"1991","journal-title":"APMIS"},{"key":"BIB30","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/hep.510300140","volume":"30","author":"Baumann","year":"1999","journal-title":"Hepatology"},{"key":"BIB31","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.284.5417.1168","volume":"284","author":"Petersen","year":"1999","journal-title":"Science"},{"key":"BIB32","doi-asserted-by":"crossref","first-page":"496a","DOI":"10.1002\/hep.510300614","volume":"30","author":"Theise","year":"1999","journal-title":"Hepatology"},{"key":"BIB33","first-page":"243","volume-title":"Pathology of the Liver","author":"Scheuer","year":"1995","unstructured":"Viral Hepatitis. In: Pathology of the Liver. 3rd ed. Edinburgh: Churchill-Livingstone. 1995; 243-268."},{"key":"BIB34","first-page":"415a","volume":"28","author":"Saxena","year":"1998","journal-title":"Hepatology"},{"key":"BIB35","doi-asserted-by":"crossref","first-page":"603a","DOI":"10.1016\/S0168-8278(98)80283-3","volume":"28","author":"Hytiroglou","year":"1998","journal-title":"Hepatology"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510300614","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199912000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:27:01Z","timestamp":1733052421000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199912000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1999]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510300614","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1999,12]]}}}