{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:02:53Z","timestamp":1791295373872,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2069,"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":[[2010,1]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Bone marrow (BM)-derived stem cells and CD34+ fibrocytes are associated with fibrogenesis in several organs. In an<\/jats:bold>\n                                 <jats:bold>\n                                    Abcb4\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mouse model for sclerosing cholangitis alpha-smooth muscle actin-positive (\u03b1-SMA+) myofibroblasts are thought to play a pivotal role in hepatic fibrogenesis. The aim of this study was 2-fold: (1) to demonstrate that the origin of an important fibrogenetic cell population is the BM; and (2) to investigate whether transplantation of BM (BM-Tx) affects liver function, staging, and grading. Surrogate markers for fibrogenesis and regulation of hepatic stellate cells (HSC) as well as progenitor-cell-derived fibrocytes in liver tissue were analyzed by quantitative real-time polymerase chain reaction (PCR) and immunohistology. After lethal irradiation of recipient mice, BM-Tx was carried out by way of tail vein injection of BM cells from marker protein donors (green fluorescent protein, GFP+) or<\/jats:bold>\n                                 <jats:bold>\n                                    Abcb4\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice as control (syngeneic Tx). Parameters of liver function were assessed serologically and histologically. Activated HSC of \u03b1-SMA+\/CRP2+ phenotype were expressed in \u224850% of proliferating bile ducts, whereas fibrotic liver parenchyma showed no expression thereof. Epithelial mesenchymal transfer (EMT) was visualized in the areas of proliferating bile ducts. The hematopoietic origin of CD34+ fibrocytes was demonstrated immunohistologically in livers of BM chimeric mice. These CD34+ cells infiltrated hepatic lobules from portal fields and developed a desmin+ phenotype expressing collagen type I in fibrotic parenchyma as well as<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>after isolation by magnetic cell separation. Transplantation of GFP+\/<\/jats:bold>\n                                 <jats:bold>\n                                    Abcb4\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    + BM improved liver function and staging compared with sham transplantation, but no significant differences were noticed among allogeneic and syngeneic Tx.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>The present study is the first to identify that both BM-derived fibrocytes and HSC are involved in biliary fibrogenesis in<\/jats:bold>\n                                 <jats:bold>\n                                    Abcb4\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice. Our data suggest that changes in immunity subsequent to BM-Tx may alter hepatic fibrosis. (Hepatology 2009.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23274","type":"journal-article","created":{"date-parts":[[2009,9,9]],"date-time":"2009-09-09T14:15:07Z","timestamp":1252505707000},"page":"267-276","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":65,"title":["Bone Marrow Transplantation Demonstrates Medullar Origin of Cd34+ Fibrocytes and Ameliorates Hepatic Fibrosis in Abcb4 \u2212\/\u2212 Mice"],"prefix":"10.1097","volume":"51","author":[{"given":"Martin","family":"Roderfeld","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Rath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Voswinckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Dierkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zahner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Roeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-32-20241201","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11605-007-0344-3","article-title":"Sclerosing cholangitis epidemiology and etiology.","volume":"12","author":"Lazaridis","year":"2008","journal-title":"J Gastrointest Surg"},{"key":"R2-32-20241201","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/j.gastro.2003.07.011","article-title":"Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community.","volume":"125","author":"Bambha","year":"2003","journal-title":"Gastroenterology"},{"key":"R3-32-20241201","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.gastro.2004.04.009","article-title":"Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice.","volume":"127","author":"Fickert","year":"2004","journal-title":"Gastroenterology"},{"key":"R4-32-20241201","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-511X-6-3","article-title":"Primary sclerosing cholangitisthe arteriosclerosis of the bile duct?","volume":"6","author":"Fickert","year":"2007","journal-title":"Lipids Health Dis"},{"key":"R5-32-20241201","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1136\/gut.2006.092742","article-title":"Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene.","volume":"56","author":"Wasmuth","year":"2007","journal-title":"Gut"},{"key":"R6-32-20241201","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0092-8674(93)90380-9","article-title":"Homozygous disruption of the murine mdr2 Pglycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease.","volume":"75","author":"Smit","year":"1993","journal-title":"Cell"},{"key":"R7-32-20241201","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jhep.2005.06.025","article-title":"Mdr2 (Abcb4) mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro and antifibrogenic genes.","volume":"43","author":"Popov","year":"2005","journal-title":"J Hepatol"},{"key":"R8-32-20241201","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF03403533","article-title":"Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair.","volume":"1","author":"Bucala","year":"1994","journal-title":"Mol Med"},{"key":"R9-32-20241201","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0002-9440(10)62289-4","article-title":"CCR2mediated recruitment of fibrocytes to the alveolar space after fibrotic injury.","volume":"166","author":"Moore","year":"2005","journal-title":"Am J Pathol"},{"key":"R10-32-20241201","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2174\/157488807781696249","article-title":"CD34 fibrocytes: morphology, histogenesis and function.","volume":"2","author":"Barth","year":"2007","journal-title":"Curr Stem Cell Res Ther"},{"key":"R11-32-20241201","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1524-475X.2008.00366.x","article-title":"Serum amyloid P inhibits dermal wound healing.","volume":"16","author":"NaikMathuria","year":"2008","journal-title":"Wound Repair Regen"},{"key":"R12-32-20241201","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1172\/JCI200420997","article-title":"Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis.","volume":"114","author":"Phillips","year":"2004","journal-title":"J Clin Invest"},{"key":"R13-32-20241201","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/sj.ki.5002325","article-title":"Fibrocytes: a new insight into kidney fibrosis.","volume":"72","author":"Wada","year":"2007","journal-title":"Kidney Int"},{"key":"R14-32-20241201","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1053\/j.gastro.2004.02.025","article-title":"A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis.","volume":"126","author":"Forbes","year":"2004","journal-title":"Gastroenterology"},{"key":"R15-32-20241201","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jhep.2006.04.014","article-title":"Bone marrowderived fibrocytes participate in pathogenesis of liver fibrosis.","volume":"45","author":"Kisseleva","year":"2006","journal-title":"J Hepatol"},{"key":"R16-32-20241201","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1053\/j.gastro.2006.01.036","article-title":"The bone marrow functionally contributes to liver fibrosis.","volume":"130","author":"Russo","year":"2006","journal-title":"Gastroenterology"},{"key":"R17-32-20241201","doi-asserted-by":"crossref","first-page":"6538","DOI":"10.1002\/pmic.200600580","article-title":"Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitis.","volume":"6","author":"Henkel","year":"2006","journal-title":"Proteomics"},{"key":"R18-32-20241201","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/hep.20022","article-title":"Spontaneous cholecysto and hepatolithiasis in Mdr2 mice: a model for low phospholipidassociated cholelithiasis.","volume":"39","author":"Lammert","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R19-32-20241201","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0014-5793(97)00313-X","article-title":"Green mice as a source of ubiquitous green cells.","volume":"407","author":"Okabe","year":"1997","journal-title":"FEBS Lett"},{"key":"R20-32-20241201","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/01.RES.0000087643.60150.C2","article-title":"Circulating vascular progenitor cells do not contribute to compensatory lung growth.","volume":"93","author":"Voswinckel","year":"2003","journal-title":"Circ Res"},{"key":"R21-32-20241201","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1097\/00000478-199512000-00007","article-title":"Chronic hepatitis. An update on terminology and reporting.","volume":"19","author":"Batts","year":"1995","journal-title":"Am J Surg Pathol"},{"key":"R22-32-20241201","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis.","volume":"22","author":"Ishak","year":"1995","journal-title":"J Hepatol"},{"key":"R23-32-20241201","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-2697(81)90261-X","article-title":"A simple method to determine nanogram levels of 4hydroxyproline in biological tissues.","volume":"112","author":"Jamall","year":"1981","journal-title":"Anal Biochem"},{"key":"R24-32-20241201","first-page":"99","article-title":"Isolation and culture of hepatic stellate cells.","volume":"117","author":"Weiskirchen","year":"2005","journal-title":"Methods Mol Med"},{"key":"R25-32-20241201","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in realtime RTPCR.","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"R26-32-20241201","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1172\/JCI17902","article-title":"HGF, SDF1, and MMP9 are involved in stressinduced human CD34 stem cell recruitment to the liver.","volume":"112","author":"Kollet","year":"2003","journal-title":"J Clin Invest"},{"key":"R27-32-20241201","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.jhep.2007.02.003","article-title":"Expression of MMPs and TIMPs in liver fibrosis a systematic review with special emphasis on antifibrotic strategies.","volume":"46","author":"Hemmann","year":"2007","journal-title":"J Hepatol"},{"key":"R28-32-20241201","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jhep.2003.10.012","article-title":"Commitment of bone marrow cells to hepatic stellate cells in mouse.","volume":"40","author":"Baba","year":"2004","journal-title":"J Hepatol"},{"key":"R29-32-20241201","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1136\/gut.2006.111617","article-title":"Human mesenchymal stem cells as a twoedged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential.","volume":"57","author":"di Bonzo","year":"2008","journal-title":"Gut"},{"key":"R31-32-20241201","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/hep.21624","article-title":"Biliary epithelialmesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis.","volume":"45","author":"Robertson","year":"2007","journal-title":"HEPATOLOGY"},{"key":"R32-32-20241201","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/labinvest.3700704","article-title":"Epithelialmesenchymal transition contributes to portal tract fibrogenesis during human chronic liver disease.","volume":"88","author":"Rygiel","year":"2008","journal-title":"Lab Invest"},{"key":"R33-32-20241201","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000113941","article-title":"Cutaneous graftversushost disease: a guide for the dermatologist.","volume":"216","author":"Hausermann","year":"2008","journal-title":"Dermatology"},{"key":"R34-32-20241201","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/81326","article-title":"Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.","volume":"6","author":"Lagasse","year":"2000","journal-title":"Nat Med"},{"key":"R35-32-20241201","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1002\/hep.20452","article-title":"Transplantation of bone marrow cells reduces CCl4induced liver fibrosis in mice.","volume":"40","author":"Sakaida","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R36-32-20241201","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nature01531","article-title":"Cell fusion is the principal source of bonemarrowderived hepatocytes.","volume":"422","author":"Wang","year":"2003","journal-title":"Nature"},{"key":"R37-32-20241201","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/hep.21015","article-title":"Hematopoietic cells as hepatocyte stem cells: a critical review of the evidence.","volume":"43","author":"Thorgeirsson","year":"2006","journal-title":"HEPATOLOGY"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23274","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201001000-00032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T13:41:08Z","timestamp":1733060468000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201001000-00032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23274","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2010,1]]}}}