Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells

BMC Immunology

Research Article

Annette Audigé¹  Sandra Ivic¹  Stefan P. Kuster¹  Duo Li¹  Audrey Fahrny¹  Roberto F. Speck¹  Mary-Aude Rochat¹  Simon Bredl¹  Erika Schlaepfer¹  Christina K. S. Muller¹  Renier Myburgh¹  Gustavo Gers-Huber¹  Alexandra U. Scherrer² 

[1] Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland;Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland;Institute of Medical Virology, University of Zurich, Zurich, Switzerland;

关键词: Hematopoiesis;    Hematopoietic stem cells;    Cord blood stem cell transplantation;    Humanized mice;    NSG mice;   

DOI  :  10.1186/s12865-017-0209-9

 received in 2016-11-18, accepted in 2017-04-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHumanized 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.ResultsHuman 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.ConclusionsOverall, 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.

【 授权许可】

CC BY   
© The Author(s). 2017