Human cord blood hematopoietic cells acquire neural features when cultured in the presence of neurogenic cytokines

We report a Human Immune System (HIS)-humanized mouse model (“DRAGA”: HLA-A2.HLA-DR4.Rag1KO.IL-2 RγcKO.NOD) for COVID-19 research. DRAGA mice express transgenically HLA-class I and class-II molecules in the mouse thymus to promote human T cell development and human B cell Ig-class switching. When infused with human hematopoietic stem cells from cord blood reconstitute a functional human immune system, as well as human epi/endothelial cells in lung and upper respiratory airways expressing the human ACE2 receptor for SARS-CoV-2. The DRAGA mice were able to sustain SARS-CoV-2 infection for at least 25 days. Infected mice showed replicating virus in the lungs, deteriorating clinical condition, and human-like lung immunopathology including human lymphocyte infiltrates, microthrombi and pulmonary sequelae. Among the intra-alveolar and peri-bronchiolar lymphocyte infiltrates, human lung-resident (CD103 + ) CD8 + and CD4 + T cells were sequestered in epithelial (CD326 + ) lung niches and secreted granzyme B and perforin, suggesting anti-viral cytotoxic activity. Infected mice also mounted human IgG antibody responses to SARS-CoV-2 viral proteins. Hence, HIS-DRAGA mice showed unique advantages as a surrogate in vivo human model for studying SARS-CoV-2 immunopathological mechanisms and testing the safety and efficacy of candidate vaccines and therapeutics.

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A Data-Centric Approach to Investigate the Feasibility of Utilizing Animal Medical Data as a Solution for Human Medical Data Scarcity

Al-Qudah,

Suen

2024

IEEE Access

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Human cord blood hematopoietic cells acquire neural features when cultured in the presence of neurogenic cytokines

Cited by 3 publications

References 32 publications

Umbilical Cord Blood Hematopoietic Cells: From Biology to Hematopoietic Transplants and Cellular Therapies

Umbilical Cord Blood Hematopoietic Cells: From Biology to Hematopoietic Transplants and Cellular Therapies

Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19

A Data-Centric Approach to Investigate the Feasibility of Utilizing Animal Medical Data as a Solution for Human Medical Data Scarcity

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