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Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells
Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, wi...
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Published in: | Stem cells (Dayton, Ohio) Ohio), 2003-01, Vol.21 (2), p.217-227 |
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creator | Kakinuma, Sei Tanaka, Yujiro Chinzei, Ryoko Watanabe, Mamoru Shimizu‐saito, Keiko Hara, Yuzuru Teramoto, Kenichi Arii, Shigeki Sato, Chifumi Takase, Kozo Yasumizu, Takehiko Teraoka, Hirobumi |
description | Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21‐day cultures expressed ALB, and the ALB+ cells coexpressed hepatocyte lineage markers. The ALB‐expressing cells were able to proliferate in the culture system. Moreover, in the cell‐transplantation model into liver‐injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB‐derived cell transplantation as a novel therapeutic option for liver failure. |
doi_str_mv | 10.1634/stemcells.21-2-217 |
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In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21‐day cultures expressed ALB, and the ALB+ cells coexpressed hepatocyte lineage markers. The ALB‐expressing cells were able to proliferate in the culture system. Moreover, in the cell‐transplantation model into liver‐injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB‐derived cell transplantation as a novel therapeutic option for liver failure.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1634/stemcells.21-2-217</identifier><identifier>PMID: 12634418</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Albumin ; Albumins - genetics ; Animals ; Biomarkers ; Cell Culture Techniques - methods ; Cell Division ; Cell Lineage ; Cell transplantation ; Cells, Cultured ; Cord blood ; Cord Blood Stem Cell Transplantation ; Fetal Blood - cytology ; Hepatectomy ; Hepatocyte ; Hepatocytes - cytology ; Humans ; Liver - cytology ; Liver - surgery ; Mice ; Mice, SCID ; Proliferation ; RNA, Messenger - analysis ; Stem Cells - cytology</subject><ispartof>Stem cells (Dayton, Ohio), 2003-01, Vol.21 (2), p.217-227</ispartof><rights>Copyright © 2003 AlphaMed Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4607-5dbc4f36c51f32fc028eb2a10bbb4cf29a7b2755fb6e68986b0059b14c98e5ee3</citedby><cites>FETCH-LOGICAL-c4607-5dbc4f36c51f32fc028eb2a10bbb4cf29a7b2755fb6e68986b0059b14c98e5ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12634418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakinuma, Sei</creatorcontrib><creatorcontrib>Tanaka, Yujiro</creatorcontrib><creatorcontrib>Chinzei, Ryoko</creatorcontrib><creatorcontrib>Watanabe, Mamoru</creatorcontrib><creatorcontrib>Shimizu‐saito, Keiko</creatorcontrib><creatorcontrib>Hara, Yuzuru</creatorcontrib><creatorcontrib>Teramoto, Kenichi</creatorcontrib><creatorcontrib>Arii, Shigeki</creatorcontrib><creatorcontrib>Sato, Chifumi</creatorcontrib><creatorcontrib>Takase, Kozo</creatorcontrib><creatorcontrib>Yasumizu, Takehiko</creatorcontrib><creatorcontrib>Teraoka, Hirobumi</creatorcontrib><title>Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21‐day cultures expressed ALB, and the ALB+ cells coexpressed hepatocyte lineage markers. The ALB‐expressing cells were able to proliferate in the culture system. Moreover, in the cell‐transplantation model into liver‐injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB‐derived cell transplantation as a novel therapeutic option for liver failure.</description><subject>Albumin</subject><subject>Albumins - genetics</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell Division</subject><subject>Cell Lineage</subject><subject>Cell transplantation</subject><subject>Cells, Cultured</subject><subject>Cord blood</subject><subject>Cord Blood Stem Cell Transplantation</subject><subject>Fetal Blood - cytology</subject><subject>Hepatectomy</subject><subject>Hepatocyte</subject><subject>Hepatocytes - cytology</subject><subject>Humans</subject><subject>Liver - cytology</subject><subject>Liver - surgery</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Proliferation</subject><subject>RNA, Messenger - analysis</subject><subject>Stem Cells - cytology</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqNkD1PwzAQhi0E4vsPMCBPbCm2YzsOG1SFIhUBosyW7V5QkBMXOxHqvydRK1hZ7m543lenB6ELSiZU5vw6ddA48D5NGM1Yxmixh46p4GXGS6r2h5tImQlSlkfoJKVPQigXSh2iI8qGPKfqGL3O-8a0-L2xta-d8Xga4grf-RBW2CRs8FvoowMcKryMpk1rb9rOWA94DmvT1Q6_xPABbd2FiKfjM2fooDI-wflun6L3-9lyOs8Wzw-P09tF5rgkRSZW1vEql07QKmeVI0yBZYYSay13FStNYVkhRGUlSFUqaQkRpaXclQoEQH6Krra96xi-ekidbuo06jAthD7pIqekULIYQLYFXQwpRaj0OtaNiRtNiR5F6l-RmlHNhjGGLnftvW1g9RfZmRuAmy3wXXvY_KNSvy1nT4ySsf0HMn2ETw</recordid><startdate>20030101</startdate><enddate>20030101</enddate><creator>Kakinuma, Sei</creator><creator>Tanaka, Yujiro</creator><creator>Chinzei, Ryoko</creator><creator>Watanabe, Mamoru</creator><creator>Shimizu‐saito, Keiko</creator><creator>Hara, Yuzuru</creator><creator>Teramoto, Kenichi</creator><creator>Arii, Shigeki</creator><creator>Sato, Chifumi</creator><creator>Takase, Kozo</creator><creator>Yasumizu, Takehiko</creator><creator>Teraoka, Hirobumi</creator><general>John Wiley & Sons, Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030101</creationdate><title>Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells</title><author>Kakinuma, Sei ; Tanaka, Yujiro ; Chinzei, Ryoko ; Watanabe, Mamoru ; Shimizu‐saito, Keiko ; Hara, Yuzuru ; Teramoto, Kenichi ; Arii, Shigeki ; Sato, Chifumi ; Takase, Kozo ; Yasumizu, Takehiko ; Teraoka, Hirobumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4607-5dbc4f36c51f32fc028eb2a10bbb4cf29a7b2755fb6e68986b0059b14c98e5ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Albumin</topic><topic>Albumins - genetics</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell Division</topic><topic>Cell Lineage</topic><topic>Cell transplantation</topic><topic>Cells, Cultured</topic><topic>Cord blood</topic><topic>Cord Blood Stem Cell Transplantation</topic><topic>Fetal Blood - cytology</topic><topic>Hepatectomy</topic><topic>Hepatocyte</topic><topic>Hepatocytes - cytology</topic><topic>Humans</topic><topic>Liver - cytology</topic><topic>Liver - surgery</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Proliferation</topic><topic>RNA, Messenger - analysis</topic><topic>Stem Cells - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kakinuma, Sei</creatorcontrib><creatorcontrib>Tanaka, Yujiro</creatorcontrib><creatorcontrib>Chinzei, Ryoko</creatorcontrib><creatorcontrib>Watanabe, Mamoru</creatorcontrib><creatorcontrib>Shimizu‐saito, Keiko</creatorcontrib><creatorcontrib>Hara, Yuzuru</creatorcontrib><creatorcontrib>Teramoto, Kenichi</creatorcontrib><creatorcontrib>Arii, Shigeki</creatorcontrib><creatorcontrib>Sato, Chifumi</creatorcontrib><creatorcontrib>Takase, Kozo</creatorcontrib><creatorcontrib>Yasumizu, Takehiko</creatorcontrib><creatorcontrib>Teraoka, Hirobumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kakinuma, Sei</au><au>Tanaka, Yujiro</au><au>Chinzei, Ryoko</au><au>Watanabe, Mamoru</au><au>Shimizu‐saito, Keiko</au><au>Hara, Yuzuru</au><au>Teramoto, Kenichi</au><au>Arii, Shigeki</au><au>Sato, Chifumi</au><au>Takase, Kozo</au><au>Yasumizu, Takehiko</au><au>Teraoka, Hirobumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2003-01-01</date><risdate>2003</risdate><volume>21</volume><issue>2</issue><spage>217</spage><epage>227</epage><pages>217-227</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21‐day cultures expressed ALB, and the ALB+ cells coexpressed hepatocyte lineage markers. The ALB‐expressing cells were able to proliferate in the culture system. Moreover, in the cell‐transplantation model into liver‐injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. 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subjects | Albumin Albumins - genetics Animals Biomarkers Cell Culture Techniques - methods Cell Division Cell Lineage Cell transplantation Cells, Cultured Cord blood Cord Blood Stem Cell Transplantation Fetal Blood - cytology Hepatectomy Hepatocyte Hepatocytes - cytology Humans Liver - cytology Liver - surgery Mice Mice, SCID Proliferation RNA, Messenger - analysis Stem Cells - cytology |
title | Human Umbilical Cord Blood as a Source of Transplantable Hepatic Progenitor Cells |
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