{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T02:28:14Z","timestamp":1781231294029,"version":"3.54.1"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells.<\/jats:p>","DOI":"10.3390\/cells8030226","type":"journal-article","created":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T11:21:59Z","timestamp":1552044119000},"page":"226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Excessive Reactive Iron Impairs Hematopoiesis by Affecting Both Immature Hematopoietic Cells and Stromal Cells"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-525X","authenticated-orcid":false,"given":"Hirokazu","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-6666","authenticated-orcid":false,"given":"J. Luis","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-9751","authenticated-orcid":false,"given":"Shinya","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ashida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuru","family":"Kanakura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1559S","DOI":"10.3945\/ajcn.117.155804","article-title":"Current understanding of iron homeostasis","volume":"106","author":"Anderson","year":"2017","journal-title":"Am. 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