A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains

Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the...

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Main Authors: Hernando Gutierrez-Barbosa, Sandra Medina-Moreno, Federico Perdomo-Celis, Harry Davis, Carolina Coronel-Ruiz, Juan C. Zapata, Joel V. Chua
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/11/6/1548
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author Hernando Gutierrez-Barbosa
Sandra Medina-Moreno
Federico Perdomo-Celis
Harry Davis
Carolina Coronel-Ruiz
Juan C. Zapata
Joel V. Chua
author_facet Hernando Gutierrez-Barbosa
Sandra Medina-Moreno
Federico Perdomo-Celis
Harry Davis
Carolina Coronel-Ruiz
Juan C. Zapata
Joel V. Chua
author_sort Hernando Gutierrez-Barbosa
collection DOAJ
description Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34<sup>+</sup> fetal cord blood from a single donor. Our results showed that all murine strains sustained human immune cells within a proinflammatory environment induced by GvHD. However, the Hu-SGM3 model consistently generated higher numbers of human T cells, monocytes, dendritic cells, mast cells, and megakaryocytes, and a low number of circulating platelets showing an activated profile when compared with the other murine strains. The hu-NOG-EXL model had a similar cell development profile but a higher number of circulating platelets with an inactivated state, and the hu-NSG and hu-NCG developed low frequencies of immune cells compared with the other models. Interestingly, only the hu-SGM3 and hu-EXL models developed mast cells. In conclusion, our findings highlight the importance of selecting the appropriate humanized mouse model for specific research questions, considering the strengths and limitations of each model and the immune cell populations of interest.
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spelling doaj.art-6388003b64634bfa8cffe0a7c67dc60b2023-11-18T11:43:26ZengMDPI AGMicroorganisms2076-26072023-06-01116154810.3390/microorganisms11061548A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse StrainsHernando Gutierrez-Barbosa0Sandra Medina-Moreno1Federico Perdomo-Celis2Harry Davis3Carolina Coronel-Ruiz4Juan C. Zapata5Joel V. Chua6Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, ColombiaInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USAVice-Chancellor of Research, Virology Group, Universidad El Bosque, Bogotá 110121, ColombiaInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USAHumanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34<sup>+</sup> fetal cord blood from a single donor. Our results showed that all murine strains sustained human immune cells within a proinflammatory environment induced by GvHD. However, the Hu-SGM3 model consistently generated higher numbers of human T cells, monocytes, dendritic cells, mast cells, and megakaryocytes, and a low number of circulating platelets showing an activated profile when compared with the other murine strains. The hu-NOG-EXL model had a similar cell development profile but a higher number of circulating platelets with an inactivated state, and the hu-NSG and hu-NCG developed low frequencies of immune cells compared with the other models. Interestingly, only the hu-SGM3 and hu-EXL models developed mast cells. In conclusion, our findings highlight the importance of selecting the appropriate humanized mouse model for specific research questions, considering the strengths and limitations of each model and the immune cell populations of interest.https://www.mdpi.com/2076-2607/11/6/1548humanizationhumanized mouse modelxenograftCD34NSGNCG
spellingShingle Hernando Gutierrez-Barbosa
Sandra Medina-Moreno
Federico Perdomo-Celis
Harry Davis
Carolina Coronel-Ruiz
Juan C. Zapata
Joel V. Chua
A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
Microorganisms
humanization
humanized mouse model
xenograft
CD34
NSG
NCG
title A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
title_full A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
title_fullStr A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
title_full_unstemmed A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
title_short A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
title_sort comparison of lymphoid and myeloid cells derived from human hematopoietic stem cells xenografted into nod derived mouse strains
topic humanization
humanized mouse model
xenograft
CD34
NSG
NCG
url https://www.mdpi.com/2076-2607/11/6/1548
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