Limitations of Busulfan to Create Humanize Mice with an Innate Immune System.

Abstract

Humanized mouse models have improved biomedical research by providing a tractable system with which to perform in vivo experiments on human tissues. Use of irritators is the standard method for establishing high levels of stem cell engraftment, however not all institutes have access to this instrumentation in the animal facility. The use of busulfan has been successfully used to precondition for stem cell engraftment on a limited number of mouse backgrounds. In this report we further test the utility of busulfan as a means to successfully engraft hIL15-Tg-NSG and SGM3-NSG mouse stains which are capable of establishing the innate NK cell and myeloid immune compartments. Results from our studies show that busulfan can successfully precondition hIL15-Tg-NSG mice but not SGM3-NSG mice for high levels of human immune cell engraftment. SGM3-NSG mice preconditioned with busulfan exhibited only 10-20% human CD45 cells in the bone marrow or spleen, where as NSG and hIL15-Tg-NSG mice routinely achieved [~]80%. Busulfan preconditioned SGM3-NSG mice showed elevated levels of granulocytic MDSC, and cDC1 and cDC2 myeloid populations. This is in contrast with hIL15-TG-NSG which showed robust reconstitution of mature CD16 expressing NK cells. We conclude from our studies that busulfan is an effective means to precondition mice for CD34+ stem cell engraftment, but it may have limitations when use to precondition the SGM3-NSG model.