Comparable human reconstitution following Cesium-137 versus X-ray irradiation preconditioning in immunodeficient NOG mice

Autor:	Martin Tolstrup, Stine Sofie Frank Nielsen, Ole Schmeltz Søgaard, Anna H. F. Andersen, Lars Østergaard, Paul W. Denton, Jakob Le Fèvre Harslund, Rikke Olesen
Rok vydání:	2020
Předmět:	0301 basic medicine Cell Transplantation Physiology Diagnostic Radiology Mice White Blood Cells 0302 clinical medicine Spectrum Analysis Techniques Animal Cells Immune Physiology Medicine and Health Sciences Blood and Lymphatic System Procedures Cytotoxic T cell Bone Marrow Transplantation Multidisciplinary medicine.diagnostic_test T Cells Radiology and Imaging Animal Models Flow Cytometry Bone Imaging medicine.anatomical_structure Phenotype Experimental Organism Systems Cesium Radioisotopes Spectrophotometry Medicine Female Lymph Cytophotometry Stem cell Cellular Types Research Article Imaging Techniques Science Immune Cells Immunology Spleen Bone Marrow Cells Surgical and Invasive Medical Procedures Mouse Models Cytotoxic T cells Thymus Gland Biology Research and Analysis Methods Flow cytometry 03 medical and health sciences Model Organisms Diagnostic Medicine medicine Animals Humans Transplantation Blood Cells X-Rays Immunity Biology and Life Sciences Cell Biology X-Ray Radiography Kinetics 030104 developmental biology Humanized mouse Cancer research Animal Studies Bone marrow Lymph Nodes 030215 immunology Stem Cell Transplantation
Zdroj:	PLoS ONE Andersen, A H F, Nielsen, S S F, Olesen, R, Harslund, J L F, Søgaard, O S, Østergaard, L, Denton, P W & Tolstrup, M 2020, ' Comparable human reconstitution following Cesium-137 versus X-ray irradiation preconditioning in immunodeficient NOG mice ', PLOS ONE, vol. 15, no. 10, e0241375 . https://doi.org/10.1371/journal.pone.0241375 PLoS ONE, Vol 15, Iss 10, p e0241375 (2020)
ISSN:	1932-6203
Popis:	Humanized mouse models are used extensively in research involving human pathogens and diseases. However, most of these models require preconditioning. Radio-active sources have been used routinely for this purpose but safety issues have motivated researchers to transition to chemical or X-ray based preconditioning. In this study, we directly compare 350 kV X-ray and Cs-137 low-dose precondition of NOG mice before human stem cell transplantation. Based on flow cytometry data, we found that engraftment of human cells into the mouse bone marrow was similar between radiation sources. Likewise, human engraftment in the peripheral blood was comparable between Cs-137 and three different X-ray doses with equal chimerization kinetics. In primary lymphoid organs such as the thymus and lymph nodes, and spleen, liver and lung, human-to-mouse chimerization was also comparable between irradiation sources. Development of different CD4 and CD8 T cells as well as these cells’ maturation stages, i.e. from naïve to effector and memory subsets were generally analogous. Based on our results, we conclude that there are no discernable differences between the two sources in the low-dose spectrum investigated. However, while we encourage the transition to X-ray-based sources, we recommend all research groups to consider technical specifications and dose-finding studies. Humanized mouse models are used extensively in research involving human pathogens and diseases. However, most of these models require preconditioning. Radio-active sources have been used routinely for this purpose but safety issues have motivated researchers to transition to chemical or X-ray based preconditioning. In this study, we directly compare 350 kV X-ray and Cs-137 low-dose precondition of NOG mice before human stem cell transplantation. Based on flow cytometry data, we found that engraftment of human cells into the mouse bone marrow was similar between radiation sources. Likewise, human engraftment in the peripheral blood was comparable between Cs-137 and three different X-ray doses with equal chimerization kinetics. In primary lymphoid organs such as the thymus and lymph nodes, and spleen, liver and lung, human-to-mouse chimerization was also comparable between irradiation sources. Development of different CD4 and CD8 T cells as well as these cells' maturation stages, i.e. from naïve to effector and memory subsets were generally analogous. Based on our results, we conclude that there are no discernable differences between the two sources in the low-dose spectrum investigated. However, while we encourage the transition to X-ray-based sources, we recommend all research groups to consider technical specifications and dose-finding studies.
Databáze:	OpenAIRE
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