Generating hematopoietic cells from human pluripotent stem cells: approaches, progress and challenges

Abstract

Human pluripotent stem cells (hPSCs) have been suggested as a potential source for the production of blood cells for clinical application. In two decades, almost all types of blood cells can be successfully generated from hPSCs through various differentiated strategies. Meanwhile, with a deeper understanding of hematopoiesis, higher efficiency of generating progenitors and precursors of blood cells from hPSCs is achieved. However, how to generate large-scale mature functional cells from hPSCs for clinical use is still difficult. In this review, we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs, and remarked their efficiency and mechanisms in producing mature functional cells. We also discussed the major challenges in hPSC-derived products of blood cells and provided some potential solutions. Our review summarized efficient, simple, and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells, which will facilitate the translation of these products into the clinic.

Keywords: Blood cells; Hematopoietic differentiation; Hematopoietic stem cells; Human pluripotent stem cells.

Fig. 1

Schematic representations of embryonic hematopoiesis in vivo. There are 3 waves of hematopoietic cell generation, including primitive, pro-definitive, and definitive HSC. Among them, the primitive hematopoietic cells, including erythrocytes, megakaryocytes and macrophages, emerge in the extraembryonic yolk sac blood islands; the pro-definitive wave of hematopoiesis occurs in the yolk sac and generates definitive erythro-myeloid progenitors (EMPs) and lymphoid-primed progenitors (LMPPs) in the yolk sac; the definitive HSCs arise in the intraembryonic aorta–gonad–mesonephros region (AGM) and migrate into the fetal liver for maturation, expansion and differentiation, then initiate mobilization to the bone marrow to supply life-long hematopoiesis

Fig. 2

Overview of current methods of inducing PSCs into blood cells in vitro and potential applications of PSCs-derived blood cells. Several differentiation methods have been developed to derive blood cells from PSCs in vitro at present: through the formation of EBs, co-culture with stromal cells and induced hematopoietic differentiation in a 3D-condition. The generated blood cells could be utilized in certain fields: (1) Drug discovery: developmental biology, host-microbe interactions, disease modeling and drug evaluation; (2) Medical treatment/therapy for clinical use, such as transplantation, personalized medicine and cell therapy