{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T05:46:47Z","timestamp":1773553607736,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labor and Welfare of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Increasing numbers of reports have described hematopoietic improvement after iron chelation therapy in iron\u2010overloaded patients. These observations indicate that excess iron could affect hematopoiesis unfavorably. To investigate how excess iron affects hematopoiesis <jats:italic>in vivo<\/jats:italic>, we generated iron\u2010overloaded mice and examined hematopoietic parameters in these mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated iron\u2010overloaded mice by injecting 200\u00a0mg of iron dextran into <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>L\/6J mice, and immature hematopoietic cells in the bone marrow were evaluated by flow cytometric analyses, colony\u2010forming assays, and bone marrow transplantation analyses. We also examined changes in molecular profiles of the hematopoietic microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Conclusions<\/jats:title><jats:p>Iron\u2010overloaded (<jats:styled-content style=\"fixed-case\">IO<\/jats:styled-content>) mice did not show significant defects in the hematopoietic data of the peripheral blood. Myeloid progenitor cells in the bone marrow were increased in <jats:styled-content style=\"fixed-case\">IO<\/jats:styled-content> mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to <jats:styled-content style=\"fixed-case\">IO<\/jats:styled-content> recipients showed delayed hematopoietic reconstitution, which indicates that excess iron impacts the hematopoietic microenvironment negatively. Microarray and quantitative <jats:styled-content style=\"fixed-case\">RT\u2010PCR<\/jats:styled-content> analyses on the bone marrow stromal cells demonstrated remarkably reduced expression of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12, <jats:styled-content style=\"fixed-case\">VCAM<\/jats:styled-content>\u20101, Kit\u2010ligand, and <jats:styled-content style=\"fixed-case\">IGF<\/jats:styled-content>\u20101 in the iron\u2010overloaded mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and increased oxidative stress was observed in the <jats:styled-content style=\"fixed-case\">IO<\/jats:styled-content> bone marrow and liver. Consequently, our findings indicate that excess iron can damage bone marrow stromal cells and other vital organs, disrupting hematopoiesis presumably by increased oxidative stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12309","type":"journal-article","created":{"date-parts":[[2014,3,14]],"date-time":"2014-03-14T19:30:25Z","timestamp":1394825425000},"page":"118-128","source":"Crossref","is-referenced-by-count":63,"title":["The bone marrow hematopoietic microenvironment is impaired in iron\u2010overloaded mice"],"prefix":"10.1111","volume":"93","author":[{"given":"Hiroshi","family":"Okabe","sequence":"first","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eisuke","family":"Uehara","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masuzu","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiya","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Medicine Jichi Medical University Shimotsuke Tochigi 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