Humanized Mice as Preclinical Models in Transplantation

Abstract

Animal models have been instrumental in our understanding of the mechanisms of rejection and the testing of novel treatment options in the context of transplantation. We have now entered an exciting era with research on humanized mice driving advances in translational studies and in our understanding of the function of human cells in response to pathogens and cancer as well as the recognition of human allogeneic tissues in vivo. In this chapter we provide a historical overview of humanized mouse models of transplantation to date, outlining the distinct strains and share our experiences in the study of human transplantation immunology.

Mouse Models in Bone Fracture Healing Research

“…Xenograft models are based on immune-deficient mice, which allow the transplantation of human cells and tissues into the murine organism without rejection [114]. This approach is commonly used to perform basic studies on human tissues, cancer development and stem cell function in a complex, living organism, but outside the human body [115,116]. Xenograft mouse models can similarly be used to study human bone biology: Recent studies demonstrated the successful generation of a bioengineered human organ bone in immune-deficient mice [117,118].…”

“…Beyond the transplantation of human tissues, immunedeficient mice can be used for engraftment of a human immune system by the injection of human hematopoietic stem cells. These chimeric mice are termed Bhumanized mice^ [115] and are generally useful to study human immune cell biology in the murine organism. Such humanized mice are used to investigate human anti-tumor immune response, infectious diseases, graftversus-host disease, autoimmunity and many other research questions [114,119].…”

Regenerative medicine in the retina: from stem cells to cell replacement therapy

“…While the first approach requires adaptation of cell culture and differentiation protocols for primate or pig cells, it provides the advantage of a similar surgical setting and allows to test additional parameters, including delivery strategies and tools, volume, concentration, and total dosage of cells, as well as the requirement for immune suppression. Humanized mouse models have been very effective in understanding the immunology of transplantation, 161 and Rag2 knockouts have been effective hosts for human embryonic stem cells (hESC)-derived photoreceptor precursors. Nevertheless, while the latter allows testing of the exact cell product to be used in the clinic, functional integration studies are limited.…”