A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells
Mice bearing ossicles containing human bone marrow stromal cells enable improved leukemia engraftment and detection of high frequencies of human leukemia-initiating cells. Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However,...
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| Veröffentlicht in: | Nature medicine 2016-07, Vol.22 (7), p.812-821 |
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| creator | Reinisch, Andreas Thomas, Daniel Corces, M Ryan Zhang, Xiaohua Gratzinger, Dita Hong, Wan-Jen Schallmoser, Katharina Strunk, Dirk Majeti, Ravindra |
| description | Mice bearing ossicles containing human bone marrow stromal cells enable improved leukemia engraftment and detection of high frequencies of human leukemia-initiating cells.
Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However, current models do not fully mimic the components of the human bone marrow (BM) microenvironment, and they enable only limited engraftment of samples from some human malignancies. Here we show that a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment, formed by
in situ
differentiation of human BM-derived mesenchymal stromal cells, enables the robust engraftment of healthy human hematopoietic stem and progenitor cells, as well as primary acute myeloid leukemia (AML) samples, at levels much greater than those in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in the detection of substantially higher leukemia-initiating cell (LIC) frequencies. We also observed robust engraftment of acute promyelocytic leukemia (APL) and myelofibrosis (MF) samples, and identified LICs in these malignancies. This humanized ossicle xenotransplantation approach provides a system for modeling a wide variety of human hematological diseases. |
| doi_str_mv | 10.1038/nm.4103 |
| format | Article |
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Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However, current models do not fully mimic the components of the human bone marrow (BM) microenvironment, and they enable only limited engraftment of samples from some human malignancies. Here we show that a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment, formed by
in situ
differentiation of human BM-derived mesenchymal stromal cells, enables the robust engraftment of healthy human hematopoietic stem and progenitor cells, as well as primary acute myeloid leukemia (AML) samples, at levels much greater than those in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in the detection of substantially higher leukemia-initiating cell (LIC) frequencies. We also observed robust engraftment of acute promyelocytic leukemia (APL) and myelofibrosis (MF) samples, and identified LICs in these malignancies. This humanized ossicle xenotransplantation approach provides a system for modeling a wide variety of human hematological diseases.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm.4103</identifier><identifier>PMID: 27213817</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/100 ; 13/106 ; 13/31 ; 631/532/1542 ; 631/532/2074 ; 631/532/2139 ; 631/532/71 ; 631/67/327 ; 64/60 ; 82/1 ; Animals ; Biomedicine ; Bone and Bones ; Bone marrow ; Bone Marrow Cells ; Bone Marrow Transplantation ; Bone Transplantation ; Cancer Research ; Cell Differentiation ; Cellular biology ; Disease Models, Animal ; Fetal Blood ; Hematology ; Hematopoiesis ; Hematopoietic Stem Cells ; Humans ; Infectious Diseases ; Leukemia ; Leukemia, Myeloid, Acute ; Leukemia, Promyelocytic, Acute ; Mesenchymal Stem Cells ; Metabolic Diseases ; Mice ; Mice, SCID ; Molecular Medicine ; Neoplasm Transplantation ; Neurosciences ; Observations ; Primary Myelofibrosis ; technical-report ; Transplantation ; Transplantation, Heterologous ; Tumor Microenvironment ; Xenotransplantation</subject><ispartof>Nature medicine, 2016-07, Vol.22 (7), p.812-821</ispartof><rights>Springer Nature America, Inc. 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c678t-8efb0b1a58043fc94c53f501ca28847e99d5b142543e9839b3ab1c743d29b2433</citedby><cites>FETCH-LOGICAL-c678t-8efb0b1a58043fc94c53f501ca28847e99d5b142543e9839b3ab1c743d29b2433</cites><orcidid>0000-0002-9182-8123</orcidid></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/27213817$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reinisch, Andreas</creatorcontrib><creatorcontrib>Thomas, Daniel</creatorcontrib><creatorcontrib>Corces, M Ryan</creatorcontrib><creatorcontrib>Zhang, Xiaohua</creatorcontrib><creatorcontrib>Gratzinger, Dita</creatorcontrib><creatorcontrib>Hong, Wan-Jen</creatorcontrib><creatorcontrib>Schallmoser, Katharina</creatorcontrib><creatorcontrib>Strunk, Dirk</creatorcontrib><creatorcontrib>Majeti, Ravindra</creatorcontrib><title>A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Mice bearing ossicles containing human bone marrow stromal cells enable improved leukemia engraftment and detection of high frequencies of human leukemia-initiating cells.
Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However, current models do not fully mimic the components of the human bone marrow (BM) microenvironment, and they enable only limited engraftment of samples from some human malignancies. Here we show that a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment, formed by
in situ
differentiation of human BM-derived mesenchymal stromal cells, enables the robust engraftment of healthy human hematopoietic stem and progenitor cells, as well as primary acute myeloid leukemia (AML) samples, at levels much greater than those in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in the detection of substantially higher leukemia-initiating cell (LIC) frequencies. We also observed robust engraftment of acute promyelocytic leukemia (APL) and myelofibrosis (MF) samples, and identified LICs in these malignancies. 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bearing ossicles containing human bone marrow stromal cells enable improved leukemia engraftment and detection of high frequencies of human leukemia-initiating cells.
Xenotransplantation models represent powerful tools for the investigation of healthy and malignant human hematopoiesis. However, current models do not fully mimic the components of the human bone marrow (BM) microenvironment, and they enable only limited engraftment of samples from some human malignancies. Here we show that a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment, formed by
in situ
differentiation of human BM-derived mesenchymal stromal cells, enables the robust engraftment of healthy human hematopoietic stem and progenitor cells, as well as primary acute myeloid leukemia (AML) samples, at levels much greater than those in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in the detection of substantially higher leukemia-initiating cell (LIC) frequencies. We also observed robust engraftment of acute promyelocytic leukemia (APL) and myelofibrosis (MF) samples, and identified LICs in these malignancies. This humanized ossicle xenotransplantation approach provides a system for modeling a wide variety of human hematological diseases.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>27213817</pmid><doi>10.1038/nm.4103</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9182-8123</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/100 13/106 13/31 631/532/1542 631/532/2074 631/532/2139 631/532/71 631/67/327 64/60 82/1 Animals Biomedicine Bone and Bones Bone marrow Bone Marrow Cells Bone Marrow Transplantation Bone Transplantation Cancer Research Cell Differentiation Cellular biology Disease Models, Animal Fetal Blood Hematology Hematopoiesis Hematopoietic Stem Cells Humans Infectious Diseases Leukemia Leukemia, Myeloid, Acute Leukemia, Promyelocytic, Acute Mesenchymal Stem Cells Metabolic Diseases Mice Mice, SCID Molecular Medicine Neoplasm Transplantation Neurosciences Observations Primary Myelofibrosis technical-report Transplantation Transplantation, Heterologous Tumor Microenvironment Xenotransplantation |
| title | A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells |
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