Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease
Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenit...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Anemia |
| Online Access: | http://dx.doi.org/10.1155/2012/387385 |
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| author | Elisabeth H. Javazon Mohamed Radhi Bagirath Gangadharan Jennifer Perry David R. Archer |
| author_facet | Elisabeth H. Javazon Mohamed Radhi Bagirath Gangadharan Jennifer Perry David R. Archer |
| author_sort | Elisabeth H. Javazon |
| collection | DOAJ |
| description | Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit+, Sca-1+, Lineage−) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G0 phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function. |
| format | Article |
| id | doaj-art-86a1fce9023a40a3a03feb517dfb0d13 |
| institution | Kabale University |
| issn | 2090-1267 2090-1275 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Anemia |
| spelling | doaj-art-86a1fce9023a40a3a03feb517dfb0d132025-02-03T01:27:32ZengWileyAnemia2090-12672090-12752012-01-01201210.1155/2012/387385387385Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell DiseaseElisabeth H. Javazon0Mohamed Radhi1Bagirath Gangadharan2Jennifer Perry3David R. Archer4Department of Biology, Morehouse College, 830 Westview Drive Southwest, Atlanta, GA 30314-3773, USADepartment of Pediatrics, UI Hospitals and Clinics, University of Iowa, 2633 Carver Pavilion, 200 Hawkins Drive, Iowa City, IA 52242, USAAflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USAAflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USAAflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USAPrevious studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit+, Sca-1+, Lineage−) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G0 phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.http://dx.doi.org/10.1155/2012/387385 |
| spellingShingle | Elisabeth H. Javazon Mohamed Radhi Bagirath Gangadharan Jennifer Perry David R. Archer Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease Anemia |
| title | Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease |
| title_full | Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease |
| title_fullStr | Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease |
| title_full_unstemmed | Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease |
| title_short | Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease |
| title_sort | hematopoietic stem cell function in a murine model of sickle cell disease |
| url | http://dx.doi.org/10.1155/2012/387385 |
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