Despite their utility, PBMC humanized mice have several limitations. One major issue is the development of [graft-vs-host disease (GVHD)](), which occurs when the human immune cells attack the host mouse tissues. This can limit the duration of experiments and affect the interpretation of results. Additionally, the absence of human-specific cytokines and growth factors can impede the full functionality of the human immune system in these mice. Researchers often address these limitations by using cytokine supplementation or genetically modifying the mice to express human cytokines.