Developed by transplantation of various types of cells to immunodeficient strains

Developed by transplantation of various types of cells to immunodeficient strains of mice. In cancer research, the biology of human tumor growth, metastasis, and angiogenesis has been evaluated in these mouse models [7,8,9]. More recently, by transplanting human hepatocytes into liver-failure immunodeficient mice (uPA/SCID), mice with human livers have been developed for the study of human infectious diseases and metabolism [10,11]. Moreover, various types of hematopoietic cells can be produced within immunodeficient NOG mice by transplanting human hematopoietic stem cells [12], allowing for the establishment of a functional human-like hematopoietic lineage [13]. These techniques have proven valuable for the in vivo study of human hematopoietic stem cell function [14], infectious disease [15], and drug discovery [16], among otherIn Vivo Tool for Assessing Hematotoxicity in Humanresearch questions. Interspecies differences in responses to toxicants are influenced greatly by the specificity and expression pattern of receptors, metabolic enzymes, and many other molecules. A human-like hematopoietic lineage may mimic the response to toxicants by human cells, and such humanized mice may therefore prove to be powerful tools for health assessment and aid in our evaluation of the hematotoxicity of various factors, while accounting for interspecies differences. Hematotoxicity is evaluated according to many factors, including decreased hematopoietic cell 18325633 counts, abnormal blood coagulation, aberrant myelopoiesis, and induction of leukemia, all of which can be caused by diverse risk Docosahexaenoyl ethanolamide site factors [17,18,19]. Toxicants, such as benzene, can differentially affect human or animal hematopoietic lineages [20,21]. Here, we took advantage of mice harboring a human-like hematopoietic lineage as a tool for assessing human hematotoxicity in vivo. These mice were established by transplanting NOG mice with human CD34+ cells (HuNOG mice). The response to benzene, a model toxicant, was measured by determining decreases in the number of leukocytes. Furthermore, we established chimeric mice by transplanting C57BL/6 mouse-derived bone marrow cells into NOG mice (Mo-NOG mice). To evaluate whether the response to benzene by TA02 web Hu-NOG mice reflected interspecies differences, the degrees of benzene-induced hematotoxicities in Mo-NOG and Hu-NOG mice were compared.All experimental protocols involving human cells and laboratory mice were reviewed and approved by the Ethical Committee for the Study of Materials from Human Beings and for Research and Welfare of Experimental Animals at the Central Research Institute of Electric Power Industry.Cell Transplantation into NOG MiceAfter a 2-week quarantine and acclimatization period, wholebody X-ray irradiation of NOG mice was performed at 2.5 Gy using an X-ray generator (MBR-320R, Hitachi Medical, Tokyo, Japan) operated at 300 kV and 10 mA with 1.0-mm aluminum and 0.5-mm copper filters at a dose ratio of 1.5 Gy/min and a focus surface distance of 550 mm. Three to five hours later, the irradiated mice were injected intravenously with human CD34+ cells or mouse Lin2 bone marrow cells suspended in MEM supplemented with 2 BSA (200 mL containing 46104 cells per mouse).Mouse GroupingDonor human or mouse cell-derived hematopoietic lineages were established in NOG mice by maintenance of the mice for about 3 months after transplantation. For grouping the mice, the properties of the peripheral blood leukocytes of both types of mice were analyzed.Developed by transplantation of various types of cells to immunodeficient strains of mice. In cancer research, the biology of human tumor growth, metastasis, and angiogenesis has been evaluated in these mouse models [7,8,9]. More recently, by transplanting human hepatocytes into liver-failure immunodeficient mice (uPA/SCID), mice with human livers have been developed for the study of human infectious diseases and metabolism [10,11]. Moreover, various types of hematopoietic cells can be produced within immunodeficient NOG mice by transplanting human hematopoietic stem cells [12], allowing for the establishment of a functional human-like hematopoietic lineage [13]. These techniques have proven valuable for the in vivo study of human hematopoietic stem cell function [14], infectious disease [15], and drug discovery [16], among otherIn Vivo Tool for Assessing Hematotoxicity in Humanresearch questions. Interspecies differences in responses to toxicants are influenced greatly by the specificity and expression pattern of receptors, metabolic enzymes, and many other molecules. A human-like hematopoietic lineage may mimic the response to toxicants by human cells, and such humanized mice may therefore prove to be powerful tools for health assessment and aid in our evaluation of the hematotoxicity of various factors, while accounting for interspecies differences. Hematotoxicity is evaluated according to many factors, including decreased hematopoietic cell 18325633 counts, abnormal blood coagulation, aberrant myelopoiesis, and induction of leukemia, all of which can be caused by diverse risk factors [17,18,19]. Toxicants, such as benzene, can differentially affect human or animal hematopoietic lineages [20,21]. Here, we took advantage of mice harboring a human-like hematopoietic lineage as a tool for assessing human hematotoxicity in vivo. These mice were established by transplanting NOG mice with human CD34+ cells (HuNOG mice). The response to benzene, a model toxicant, was measured by determining decreases in the number of leukocytes. Furthermore, we established chimeric mice by transplanting C57BL/6 mouse-derived bone marrow cells into NOG mice (Mo-NOG mice). To evaluate whether the response to benzene by Hu-NOG mice reflected interspecies differences, the degrees of benzene-induced hematotoxicities in Mo-NOG and Hu-NOG mice were compared.All experimental protocols involving human cells and laboratory mice were reviewed and approved by the Ethical Committee for the Study of Materials from Human Beings and for Research and Welfare of Experimental Animals at the Central Research Institute of Electric Power Industry.Cell Transplantation into NOG MiceAfter a 2-week quarantine and acclimatization period, wholebody X-ray irradiation of NOG mice was performed at 2.5 Gy using an X-ray generator (MBR-320R, Hitachi Medical, Tokyo, Japan) operated at 300 kV and 10 mA with 1.0-mm aluminum and 0.5-mm copper filters at a dose ratio of 1.5 Gy/min and a focus surface distance of 550 mm. Three to five hours later, the irradiated mice were injected intravenously with human CD34+ cells or mouse Lin2 bone marrow cells suspended in MEM supplemented with 2 BSA (200 mL containing 46104 cells per mouse).Mouse GroupingDonor human or mouse cell-derived hematopoietic lineages were established in NOG mice by maintenance of the mice for about 3 months after transplantation. For grouping the mice, the properties of the peripheral blood leukocytes of both types of mice were analyzed.