Improvements on Humanized NOD/SCID lL-2rg-/- Mice

Abstract

Humanized mice offer a platform to study human diseases in vivo. Although progress has been made to improve human cell engraftment, the limited number of HSCs from cord blood, and the poor reconstitution and function of human monocytes/macrophages still remain as major limitations in current NSG mice.

To overcome these problems, we first developed a robust co-culture system wherein cord blood CD133+CD34+ cells were co-cultured with MSCs engineered to express Angptl5 in cytokine supplemented media. This method eliminates the variations among different units of cord blood and makes large-scale experiments possible. The poor engraftment and function of human macrophages in NSG mice were corrected by a single injection of plasmids encoding human M-CSF. With the engraftment of human tissue macrophages in NSG mice, we not only open a door for the study of human macrophages in vivo, but also make the humanized mice one step closer to clinical applications.