Progress and challenges in generating functional hematopoietic stem/progenitor cells from human pluripotent stem cells

The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) in vitro holds great potential for providing alternative sources of donor cells for clinical HSC transplantation. However, the low efficiency of current protocols for generating blood lineages and the dysfunction identified in hPSC-derived hematopoietic cells limit their use for full hematopoietic reconstitution in clinics. This review outlines the current understanding of in vitro hematopoietic differentiation from hPSCs, emphasizes the intrinsic and extrinsic molecular mechanisms that are attributed to the aberrant phenotype and function in hPSC-derived hematopoietic cells, pinpoints the current challenges to develop the truly functional HSCs from hPSCs for clinical applications and explores their potential solutions.