Document Type

Article

Publication Date

3-15-2024

Keywords

JGM, JMG, SS1

JAX Source

iScience. 2024;27(3):109238

ISSN

2589-0042

PMID

38433905

DOI

https://doi.org/10.1016/j.isci.2024.109238

Grant

This work was sup- ported by grants from The Jackson Laboratory Director Innovation Fund and NIH (P30 CA034196, R01 CA219880, and R21 OD032454)

Abstract

Pre-clinical use of humanized mice transplanted with CD34 + hematopoietic stem and progenitor cells (HSPCs) is limited by insufficient engraftment with adult non-mobilized HSPCs. Here, we developed a novel immunodeficient mice based on NOD SCID II2gc/(NSG) mice to support long-term engraftment with human adult HSPCs. As both Flt3L and IL-6 are critical for many aspects of hematopoiesis, we knock- out mouse Flt3 and knock-in human IL6 gene. The resulting mice showed an increase in the availability of mouse Flt3L to human cells and a dose-dependent production of human IL-6 upon activation. Upon transplantation with low number of human HSPCs from adult bone marrow, these humanized mice demon- strated a significantly higher engraftment with multilineage differentiation of human lymphoid and myeloid cells, and tissue colonization at one year after adult HSPC transplant. Thus, these mice enable studies of human hematopoiesis and tissue colonization over time and may facilitate building autologous models for immuno-oncology studies.

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Download

Share

COinS