Progress in construction of mouse models to investigate the pathogenesis and immune therapy of human hematological malignancy

Abstract

Hematological malignancy is a disease arisen by complicate reasons that seriously endangers human health. The research on its pathogenesis and therapies depends on the usage of animal models. Conventional animal model cannot faithfully mirror some characteristics of human features due to the evolutionary divergence, whereas the mouse models hosting human hematological malignancy are more and more applied in basic as well as translational investigations in recent years. According to the construction methods, they can be divided into different types (e.g. cell-derived xenograft (CDX) and patient-derived xenograft model (PDX) model) that have diverse characteristics and application values. In addition, a variety of strategies have been developed to improve human hematological malignant cell engraftment and differentiation in vivo. Moreover, the humanized mouse model with both functional human immune system and autologous human hematological malignancy provides a unique tool for the evaluation of the efficacy of novel immunotherapeutic drugs/approaches. Herein, we first review the evolution of the mouse model of human hematological malignancy; Then, we analyze the characteristics of different types of models and summarize the ways to improve the models; Finally, the way and value of humanized mouse model of human immune system in the immunotherapy of human hematological malignancy are discussed.

Generation of natural killer and myeloid cells in a 3D artificial marrow organoid system

“…Moreover, ideally such model should be easy to use, fast, reproducible and cheap. A wide range of in vivo models have been developed but all face some major drawbacks in term of insufficient transferability to human beings (no immunological context), the poor engraftment of hematopoietic stem and progenitor cells (HSPC) into recipient mice and high technical complexity 1,2 . Therefore, 2D in vitro models are still widely used, due to their relative simplicity, cheapness, reproducibility but missing the spatial organization and biomechanical forces of the BMM, crucial for the cellular fate.…”