Modeling myeloid cell development in health and disease using induced pluripotent stem cells
The pioneering discovery by Yamanaka and colleagues enabling the reprogramming of terminally differentiated somatic cells into induced pluripotent stem cells (iPSCs) has opened transformative opportunities for disease modeling and regenerative medicine, particularly in the context of inherited monogenic disorders. Patient-specific iPSCs can be generated, expanded almost indefinitely, and differentiated into a broad spectrum of cell types, including hematopoietic stem and progenitor cells, mature myeloid cells, and leukemic cells. Despite important limitations – such as epigenetic memory, variable differentiation efficiency, and concerns regarding tumorigenicity – iPSCs have become an indispensable experimental platform for studying inherited hematological disorders and malignancies, providing a renewable and physiologically relevant source of cells for downstream analyses. Beyond their research applications, iPSC-derived blood cells are increasingly being explored in preclinical studies and early-phase clinical trials as potential therapeutic products. The advent of CRISPR/Cas9 genome editing, pioneered by Charpentier and Doudna, has further advanced iPSC-based models by enabling precise correction or introduction of disease-causing mutations and the generation of isogenic control lines. This approach facilitates detailed mechanistic studies of defective hematopoiesis, enables drug discovery and repurposing through in silico screening platforms – such as L1000CDS2 and the Connectivity Map – and supports preclinical therapeutic validation. In this review, we summarize key applications of iPSC technology in hemato-oncology, discuss its major advantages and current limitations, and highlight emerging directions, including scalable iPSC-derived blood cell therapies for inherited and acquired bone marrow failure syndromes and leukemia.