Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells
Abstract Background Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore charact...
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doaj-0465728cd8b44465909cae29aed93bed2020-11-25T03:37:34ZengBMCBMC Immunology1471-21722017-05-0118111510.1186/s12865-017-0209-9Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cellsAnnette Audigé0Mary-Aude Rochat1Duo Li2Sandra Ivic3Audrey Fahrny4Christina K. S. Muller5Gustavo Gers-Huber6Renier Myburgh7Simon Bredl8Erika Schlaepfer9Alexandra U. Scherrer10Stefan P. Kuster11Roberto F. Speck12Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of ZurichAbstract Background Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. Results Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. Conclusions Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.http://link.springer.com/article/10.1186/s12865-017-0209-9HematopoiesisHematopoietic stem cellsCord blood stem cell transplantationHumanized miceNSG mice |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Annette Audigé Mary-Aude Rochat Duo Li Sandra Ivic Audrey Fahrny Christina K. S. Muller Gustavo Gers-Huber Renier Myburgh Simon Bredl Erika Schlaepfer Alexandra U. Scherrer Stefan P. Kuster Roberto F. Speck |
spellingShingle |
Annette Audigé Mary-Aude Rochat Duo Li Sandra Ivic Audrey Fahrny Christina K. S. Muller Gustavo Gers-Huber Renier Myburgh Simon Bredl Erika Schlaepfer Alexandra U. Scherrer Stefan P. Kuster Roberto F. Speck Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells BMC Immunology Hematopoiesis Hematopoietic stem cells Cord blood stem cell transplantation Humanized mice NSG mice |
author_facet |
Annette Audigé Mary-Aude Rochat Duo Li Sandra Ivic Audrey Fahrny Christina K. S. Muller Gustavo Gers-Huber Renier Myburgh Simon Bredl Erika Schlaepfer Alexandra U. Scherrer Stefan P. Kuster Roberto F. Speck |
author_sort |
Annette Audigé |
title |
Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells |
title_short |
Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells |
title_full |
Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells |
title_fullStr |
Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells |
title_full_unstemmed |
Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells |
title_sort |
long-term leukocyte reconstitution in nsg mice transplanted with human cord blood hematopoietic stem and progenitor cells |
publisher |
BMC |
series |
BMC Immunology |
issn |
1471-2172 |
publishDate |
2017-05-01 |
description |
Abstract Background Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. Results Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. Conclusions Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice. |
topic |
Hematopoiesis Hematopoietic stem cells Cord blood stem cell transplantation Humanized mice NSG mice |
url |
http://link.springer.com/article/10.1186/s12865-017-0209-9 |
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