5-Androstene-3β,17β-diol Promotes Recovery of Immature Hematopoietic Cells Following Myelosuppressive Radiation and Synergizes With Thrombopoietin
| Autor: | Fatima S.F. Aerts-Kaya, Dwight R. Stickney, Gerard Wagemaker, James M. Frincke, Shazia Arshad, Trudi P. Visser, Chris L. Reading |
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| Přispěvatelé: | Hematology |
| Rok vydání: | 2012 |
| Předmět: |
Androstenediol
Cancer Research Bone Marrow Cells Spleen Granulocyte Colony-Forming Units Assay Blood cell Mice Bone Marrow Granulocyte Colony-Stimulating Factor Animals Medicine Radiology Nuclear Medicine and imaging Progenitor cell Thrombopoietin Mice Inbred BALB C Blood Cells Radiation business.industry Drug Synergism Total body irradiation Hematopoietic Stem Cells Haematopoiesis medicine.anatomical_structure Oncology Radiology Nuclear Medicine and imaging Immunology Cancer research Drug Therapy Combination Dose Fractionation Radiation Bone marrow business Whole-Body Irradiation |
| Zdroj: | International Journal of Radiation Oncology Biology Physics, 84(3), E401-E407. Elsevier Inc. |
| ISSN: | 0360-3016 |
| Popis: | Purpose 5-Androstene-3β,17β-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO. |
| Databáze: | OpenAIRE |
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