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Identification of novel circulating human embryonic blood stem cells
Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would s...
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Published in: | Blood 2000-09, Vol.96 (5), p.1740-1747 |
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creator | Gallacher, Lisa Murdoch, Barbara Wu, Dongmei Karanu, Francis Fellows, Fraser Bhatia, Mickie |
description | Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies. |
doi_str_mv | 10.1182/blood.V96.5.1740 |
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These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V96.5.1740</identifier><identifier>PMID: 10961872</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>ADP-ribosyl Cyclase ; ADP-ribosyl Cyclase 1 ; Animals ; Antigens, CD - analysis ; Antigens, CD34 - analysis ; Antigens, Differentiation - analysis ; Biological and medical sciences ; Cell differentiation, maturation, development, hematopoiesis ; Cell Division ; Cell Lineage ; Cell physiology ; Colony-Forming Units Assay ; Fetal Blood - cytology ; Fetal Blood - immunology ; Fetus ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - immunology ; Humans ; Immunophenotyping ; Leukocytes, Mononuclear - cytology ; Leukocytes, Mononuclear - immunology ; Membrane Glycoproteins ; Mice ; Mice, SCID ; Molecular and cellular biology ; NAD+ Nucleosidase - analysis ; Transplantation, Heterologous</subject><ispartof>Blood, 2000-09, Vol.96 (5), p.1740-1747</ispartof><rights>2000 The American Society of Hematology</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c290t-5d89c982cc4ad01e82809ddb5ff25d3b4b4a74bb938750a6f853a1e5f659d2873</citedby><cites>FETCH-LOGICAL-c290t-5d89c982cc4ad01e82809ddb5ff25d3b4b4a74bb938750a6f853a1e5f659d2873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006497120544480$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1483744$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10961872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gallacher, Lisa</creatorcontrib><creatorcontrib>Murdoch, Barbara</creatorcontrib><creatorcontrib>Wu, Dongmei</creatorcontrib><creatorcontrib>Karanu, Francis</creatorcontrib><creatorcontrib>Fellows, Fraser</creatorcontrib><creatorcontrib>Bhatia, Mickie</creatorcontrib><title>Identification of novel circulating human embryonic blood stem cells</title><title>Blood</title><addtitle>Blood</addtitle><description>Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. Taken together, these studies demonstrate the existence of unique circulating stem cells in early human embryonic development that provide a novel and previously unexplored source of pluripotent stem cell targets for cellular and gene-based fetal therapies.</description><subject>ADP-ribosyl Cyclase</subject><subject>ADP-ribosyl Cyclase 1</subject><subject>Animals</subject><subject>Antigens, CD - analysis</subject><subject>Antigens, CD34 - analysis</subject><subject>Antigens, Differentiation - analysis</subject><subject>Biological and medical sciences</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Division</subject><subject>Cell Lineage</subject><subject>Cell physiology</subject><subject>Colony-Forming Units Assay</subject><subject>Fetal Blood - cytology</subject><subject>Fetal Blood - immunology</subject><subject>Fetus</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - immunology</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Membrane Glycoproteins</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Molecular and cellular biology</subject><subject>NAD+ Nucleosidase - analysis</subject><subject>Transplantation, Heterologous</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNp1kE1P3DAQhq2qVdnS3jmhHCpu2Y4dO7Z7q4BSJKReWq6WY4-pq8QGO0Hi35NlV2ovnEYaPe98PIScUNhSqtiXYczZb291vxVbKjm8IRsqmGoBGLwlGwDoW64lPSIfav0LQHnHxHtyREH3VEm2IRfXHtMcQ3R2jjk1OTQpP-LYuFjcMq7NdNf8WSabGpyG8pRTdM3L2qbOODUOx7F-JO-CHSt-OtRj8vv75a_zH-3Nz6vr8283rWMa5lZ4pZ1WzDluPVBUTIH2fhAhMOG7gQ_cSj4MulNSgO2DEp2lKEIvtGdKdsfkbD_3vuSHBetsplh3F9iEealGMka57MUKwh50JddaMJj7EidbngwFszNnXl4wqzkjzM7cGjk9zF6GCf1_gb2qFfh8AGx1dgzFJhfrP46rTnK-Yl_3GK4iHiMWU13E5NDHgm42PsfXj3gGEsyLzQ</recordid><startdate>20000901</startdate><enddate>20000901</enddate><creator>Gallacher, Lisa</creator><creator>Murdoch, Barbara</creator><creator>Wu, Dongmei</creator><creator>Karanu, Francis</creator><creator>Fellows, Fraser</creator><creator>Bhatia, Mickie</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>20000901</creationdate><title>Identification of novel circulating human embryonic blood stem cells</title><author>Gallacher, Lisa ; Murdoch, Barbara ; Wu, Dongmei ; Karanu, Francis ; Fellows, Fraser ; Bhatia, Mickie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c290t-5d89c982cc4ad01e82809ddb5ff25d3b4b4a74bb938750a6f853a1e5f659d2873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>ADP-ribosyl Cyclase</topic><topic>ADP-ribosyl Cyclase 1</topic><topic>Animals</topic><topic>Antigens, CD - analysis</topic><topic>Antigens, CD34 - analysis</topic><topic>Antigens, Differentiation - analysis</topic><topic>Biological and medical sciences</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Division</topic><topic>Cell Lineage</topic><topic>Cell physiology</topic><topic>Colony-Forming Units Assay</topic><topic>Fetal Blood - cytology</topic><topic>Fetal Blood - immunology</topic><topic>Fetus</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - immunology</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Membrane Glycoproteins</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Molecular and cellular biology</topic><topic>NAD+ Nucleosidase - analysis</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gallacher, Lisa</creatorcontrib><creatorcontrib>Murdoch, Barbara</creatorcontrib><creatorcontrib>Wu, Dongmei</creatorcontrib><creatorcontrib>Karanu, Francis</creatorcontrib><creatorcontrib>Fellows, Fraser</creatorcontrib><creatorcontrib>Bhatia, Mickie</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gallacher, Lisa</au><au>Murdoch, Barbara</au><au>Wu, Dongmei</au><au>Karanu, Francis</au><au>Fellows, Fraser</au><au>Bhatia, Mickie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of novel circulating human embryonic blood stem cells</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2000-09-01</date><risdate>2000</risdate><volume>96</volume><issue>5</issue><spage>1740</spage><epage>1747</epage><pages>1740-1747</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Using murine models, primitive hematopoietic cells capable of repopulation have been shown to reside in various anatomic locations, including the aortic gonad mesonephros, fetal liver, and bone marrow. These sites are thought to be seeded by stem cells migrating through fetal circulation and would serve as ideal targets for in utero cellular therapy. In humans, however, it is unknown whether similar stem cells exist. Here, we identify circulating hematopoeitic cells present during human in utero development that are capable of multilineage repopulation in immunodeficient NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Using limiting dilution analysis, the frequency of these fetal stem cells was found to be 1 in 3.2 × 105, illustrating a 3- and 22-fold enrichment compared with full-term human cord blood and circulating adult mobilized–peripheral blood, respectively. Comparison of in vivo differentiation and proliferative capacity demonstrated that circulating fetal stem cells are intrinsically distinct from hematopoietic stem cells found later in human development and those derived from the fetal liver or fetal bone marrow compartment at equivalent gestation. 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subjects | ADP-ribosyl Cyclase ADP-ribosyl Cyclase 1 Animals Antigens, CD - analysis Antigens, CD34 - analysis Antigens, Differentiation - analysis Biological and medical sciences Cell differentiation, maturation, development, hematopoiesis Cell Division Cell Lineage Cell physiology Colony-Forming Units Assay Fetal Blood - cytology Fetal Blood - immunology Fetus Flow Cytometry Fundamental and applied biological sciences. Psychology Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - immunology Humans Immunophenotyping Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - immunology Membrane Glycoproteins Mice Mice, SCID Molecular and cellular biology NAD+ Nucleosidase - analysis Transplantation, Heterologous |
title | Identification of novel circulating human embryonic blood stem cells |
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