Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells.

Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogens, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cells (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain HSCs for long-term survival. Thus, we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.