Characterization of Human Engraftment and Hemophagocytic Lymphohistiocytosis in NSG-SGM3 Neonate Mice Engrafted with Purified CD34+ Hematopoietic Stem Cells

Liam J O'Brien; Carina M Walpole; Ingrid M Leal-Rojas; Svetlana Shatunova; Andrew Moore; Ingrid G Winkler; Camille Guillerey; Kristen J Radford

doi:10.1016/j.exphem.2023.11.008

Characterization of Human Engraftment and Hemophagocytic Lymphohistiocytosis in NSG-SGM3 Neonate Mice Engrafted with Purified CD34⁺ Hematopoietic Stem Cells

Exp Hematol. 2024 Feb:130:104134. doi: 10.1016/j.exphem.2023.11.008. Epub 2023 Dec 4.

Authors

Liam J O'Brien¹, Carina M Walpole², Ingrid M Leal-Rojas², Svetlana Shatunova², Andrew Moore³, Ingrid G Winkler², Camille Guillerey², Kristen J Radford⁴

Affiliations

¹ Mater Research, The University of Queensland, Woolloongabba, Queensland, Australia. Electronic address: liam.obrien@mater.uq.edu.au.
² Mater Research, The University of Queensland, Woolloongabba, Queensland, Australia.
³ Children's Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Oncology Service, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia.
⁴ Mater Research, The University of Queensland, Woolloongabba, Queensland, Australia. Electronic address: kristen.radford@mater.uq.edu.au.

PMID: 38052261
DOI: 10.1016/j.exphem.2023.11.008

Abstract

Immunodeficient mice bearing human immune systems, or "humanized" chimeric mice, are widely used in basic research, along with the preclinical stages of drug development. Nonobese diabetic-severe combined immunodeficiency (NOD-SCID) IL2Rγ^null (NSG) mice expressing human stem cell factor, granulocyte-macrophage colony stimulating factor, and interleukin-3 (NSG-SGM3) support robust development of human myeloid cells and T cells but have reduced longevity due to the development of fatal hemophagocytic lymphohistiocytosis (HLH). Here, we describe an optimized protocol for development of human immune chimerism in NSG-SGM3 mice. We demonstrate that efficient human CD45⁺ reconstitution can be achieved and HLH delayed by engraftment of neonatal NSG-SGM3 with low numbers of human umbilical cord-derived CD34⁺ hematopoietic stem cells in the absence of preconditioning irradiation.

MeSH terms

Animals
Antigens, CD34
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells
Humans
Infant, Newborn
Lymphohistiocytosis, Hemophagocytic* / therapy
Mice
Mice, Inbred NOD
Mice, SCID
T-Lymphocytes

Substances

Antigens, CD34