Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem progenitor cells in xenotransplanted NOD SCID mouse model
Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/P...
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description | Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/PCs with rHuSCF on human cell engraftment rates in xenotransplanted NOD/SCID mouse model. The human cell engraftment rates in xenotransplanted primary and secondary NOD/SCID mice were characterized using four-color flow cytometric analysis and progenitor assay. Grafts of rHuSCF-treated UCB CD34(+) cells resulted in significantly higher levels of human cell engraftment than that of nontreated ones in both xenotransplanted primary and secondary NOD/SCID recipients. Fresh UCB CD34(+) cells did not express either of the matrix metalloproteinase (MMP) family members MMP-2 or MMP-9. rHuSCF-treated UCB CD34(+) cells expressed significant levels of MMP-2 and MMP-9. Pretreatment of UCB CD34(+) cells with the specific MMP inhibitor completely blocked human cell engraftment in xenotransplanted NOD/SCID recipients. Our results indicate that ex vivo manipulation of human HS/PCs with rHuSCF might provide an optimal approach to develop more effective stem cell-based therapies in situations where engraftment is delayed due to limiting HS/PCs number, for example, UCB transplantation. |
doi_str_mv | 10.1038/sj.bmt.1704751 |
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C</creator><creatorcontrib>ZHENG, Y ; SUN, A ; HAN, Z. C</creatorcontrib><description>Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/PCs with rHuSCF on human cell engraftment rates in xenotransplanted NOD/SCID mouse model. The human cell engraftment rates in xenotransplanted primary and secondary NOD/SCID mice were characterized using four-color flow cytometric analysis and progenitor assay. Grafts of rHuSCF-treated UCB CD34(+) cells resulted in significantly higher levels of human cell engraftment than that of nontreated ones in both xenotransplanted primary and secondary NOD/SCID recipients. Fresh UCB CD34(+) cells did not express either of the matrix metalloproteinase (MMP) family members MMP-2 or MMP-9. rHuSCF-treated UCB CD34(+) cells expressed significant levels of MMP-2 and MMP-9. Pretreatment of UCB CD34(+) cells with the specific MMP inhibitor completely blocked human cell engraftment in xenotransplanted NOD/SCID recipients. Our results indicate that ex vivo manipulation of human HS/PCs with rHuSCF might provide an optimal approach to develop more effective stem cell-based therapies in situations where engraftment is delayed due to limiting HS/PCs number, for example, UCB transplantation.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/sj.bmt.1704751</identifier><identifier>PMID: 15543197</identifier><identifier>CODEN: BMTRE9</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antigens, CD34 ; Biological and medical sciences ; Blood ; Bone marrow ; Bone marrow, stem cells transplantation. Graft versus host reaction ; CD34 antigen ; Cell Culture Techniques ; Cell Movement ; Cord blood ; Cord Blood Stem Cell Transplantation - methods ; Flow cytometry ; Gelatinase A ; Gelatinase B ; Graft Survival ; Hematopoietic stem cells ; Humans ; Immunophenotyping ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - analysis ; Matrix Metalloproteinase 9 - analysis ; Matrix metalloproteinases ; Medical sciences ; Metalloproteinase ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Models, Animal ; Progenitor cells ; Stem cell factor ; Stem Cell Factor - pharmacology ; Stem cell transplantation ; Stem cells ; Transfusions. Complications. Transfusion reactions. 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C</creatorcontrib><title>Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem progenitor cells in xenotransplanted NOD SCID mouse model</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><description>Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/PCs with rHuSCF on human cell engraftment rates in xenotransplanted NOD/SCID mouse model. The human cell engraftment rates in xenotransplanted primary and secondary NOD/SCID mice were characterized using four-color flow cytometric analysis and progenitor assay. Grafts of rHuSCF-treated UCB CD34(+) cells resulted in significantly higher levels of human cell engraftment than that of nontreated ones in both xenotransplanted primary and secondary NOD/SCID recipients. Fresh UCB CD34(+) cells did not express either of the matrix metalloproteinase (MMP) family members MMP-2 or MMP-9. rHuSCF-treated UCB CD34(+) cells expressed significant levels of MMP-2 and MMP-9. Pretreatment of UCB CD34(+) cells with the specific MMP inhibitor completely blocked human cell engraftment in xenotransplanted NOD/SCID recipients. Our results indicate that ex vivo manipulation of human HS/PCs with rHuSCF might provide an optimal approach to develop more effective stem cell-based therapies in situations where engraftment is delayed due to limiting HS/PCs number, for example, UCB transplantation.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antigens, CD34</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Bone marrow, stem cells transplantation. Graft versus host reaction</subject><subject>CD34 antigen</subject><subject>Cell Culture Techniques</subject><subject>Cell Movement</subject><subject>Cord blood</subject><subject>Cord Blood Stem Cell Transplantation - methods</subject><subject>Flow cytometry</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Graft Survival</subject><subject>Hematopoietic stem cells</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - analysis</subject><subject>Matrix Metalloproteinase 9 - analysis</subject><subject>Matrix metalloproteinases</subject><subject>Medical sciences</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Models, Animal</subject><subject>Progenitor cells</subject><subject>Stem cell factor</subject><subject>Stem Cell Factor - pharmacology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transfusions. 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Graft versus host reaction</topic><topic>CD34 antigen</topic><topic>Cell Culture Techniques</topic><topic>Cell Movement</topic><topic>Cord blood</topic><topic>Cord Blood Stem Cell Transplantation - methods</topic><topic>Flow cytometry</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Graft Survival</topic><topic>Hematopoietic stem cells</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - analysis</topic><topic>Matrix Metalloproteinase 9 - analysis</topic><topic>Matrix metalloproteinases</topic><topic>Medical sciences</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Models, Animal</topic><topic>Progenitor cells</topic><topic>Stem cell factor</topic><topic>Stem Cell Factor - pharmacology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transfusions. Complications. Transfusion reactions. 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C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem progenitor cells in xenotransplanted NOD SCID mouse model</atitle><jtitle>Bone marrow transplantation (Basingstoke)</jtitle><addtitle>Bone Marrow Transplant</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>35</volume><issue>2</issue><spage>137</spage><epage>142</epage><pages>137-142</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><coden>BMTRE9</coden><abstract>Poor in vivo homing capacity of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) can be reversed by short-term ex vivo manipulation with recombinant human stem cell factor (rHuSCF). This study was designed to evaluate the effect of ex vivo manipulation of UCB-derived HS/PCs with rHuSCF on human cell engraftment rates in xenotransplanted NOD/SCID mouse model. The human cell engraftment rates in xenotransplanted primary and secondary NOD/SCID mice were characterized using four-color flow cytometric analysis and progenitor assay. Grafts of rHuSCF-treated UCB CD34(+) cells resulted in significantly higher levels of human cell engraftment than that of nontreated ones in both xenotransplanted primary and secondary NOD/SCID recipients. Fresh UCB CD34(+) cells did not express either of the matrix metalloproteinase (MMP) family members MMP-2 or MMP-9. rHuSCF-treated UCB CD34(+) cells expressed significant levels of MMP-2 and MMP-9. Pretreatment of UCB CD34(+) cells with the specific MMP inhibitor completely blocked human cell engraftment in xenotransplanted NOD/SCID recipients. Our results indicate that ex vivo manipulation of human HS/PCs with rHuSCF might provide an optimal approach to develop more effective stem cell-based therapies in situations where engraftment is delayed due to limiting HS/PCs number, for example, UCB transplantation.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>15543197</pmid><doi>10.1038/sj.bmt.1704751</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antigens, CD34 Biological and medical sciences Blood Bone marrow Bone marrow, stem cells transplantation. Graft versus host reaction CD34 antigen Cell Culture Techniques Cell Movement Cord blood Cord Blood Stem Cell Transplantation - methods Flow cytometry Gelatinase A Gelatinase B Graft Survival Hematopoietic stem cells Humans Immunophenotyping Matrix metalloproteinase Matrix Metalloproteinase 2 - analysis Matrix Metalloproteinase 9 - analysis Matrix metalloproteinases Medical sciences Metalloproteinase Mice Mice, Inbred NOD Mice, SCID Models, Animal Progenitor cells Stem cell factor Stem Cell Factor - pharmacology Stem cell transplantation Stem cells Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplantation Transplantation, Heterologous - methods Umbilical cord Xenografts |
title | Stem cell factor improves SCID-repopulating activity of human umbilical cord blood-derived hematopoietic stem progenitor cells in xenotransplanted NOD SCID mouse model |
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