Understanding erythroid physiology and pathology in humanized mice: A closer look

Erythropoiesis, the process of red blood cell (RBC) development from haematopoietic stem cells, is crucial in haematology research due to its intricate regulation and implications in various pathologies such as anaemia and haemoglobinopathies. Humanized mice, created by introducing human cells or tissues into immunodeficient mice, offer a promising avenue in vivo approach. However, challenges persist in fully replicating human erythropoiesis in these models, particularly in generating mature human RBCs capable of sustained circulation. This review discusses the differences between human and mouse erythropoiesis, recent progress made using refined humanized mouse models for studying human erythropoiesis and erythropoietic disorders, the challenges that impede a faithful mimicking of human phenotypes in these mice and recommendations for future research improvements. Despite progress being made, enhancing the translational potential of humanized mouse models for human erythropoiesis research remains a priority.