Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells: potential, challenges, and future perspectives

Hematopoietic stem and progenitor cells (HSPCs) are responsible for the lifetime dynamics of hematopoiesis, as they are well known for their self-renewing ability and multipotency to differentiate into all types of blood cells, including both myeloid and lymphoid lineages. However, due to their limited amount and accessibility, there is a strong need to search out alternative methods to produce HSPCs. In this review, we suggest induced pluripotent stem cells (iPSCs) as a new viable source for HSPC production because these cells have the potential to self-renew while being relatively easy to modify. Recent studies have revealed that the recapitulation of definitive hematopoiesis is the key to the successful in vitro production of HSPCs with multilineage potential. Therefore, we summarized recent progress in establishing the generation of definitive HSPCs with high maturity and functionality in vitro. Definitive HSPCs can be used in disease modeling and gene therapy for genetic blood disorders via gene modification in iPSCs, applied in cellular immunotherapy in the form of a universal chimeric antigen receptor system, and may recapitulate the intricate immune system within the iPSC-derived organoids that closely mimic the in vivo pathophysiological environment. In summary, this review provides an overview of the generation of HSPCs from iPSCs, in terms of the developmental process of hematopoiesis, in vitro attempts to produce iPSC-derived definitive HSPCs, and the following applications of these cells in numerous areas. This review sheds light on the concept of iPSC-derived definitive HSPCs, setting a milestone for artificial blood production in the near future.