Towards hematopoietic reconstitution from embryonic stem cells: a sanguine future

To review recent progress towards the derivation of hematopoietic stem cells (HSCs) and blood lineages from embryonic stem cells (ESCs), and to highlight the hurdles that must be overcome in order to move the field closer to a clinical application.

Hematopoietic repopulating cells, red blood cells, and T cells have recently been derived from both murine and human ESCs. Although these results are encouraging, several outstanding issues remain to be addressed by the field before realizing clinical applicability: the phenotype of the ESC-derived HSC must be characterized, methods to purge residual teratoma-forming cells from differentiated populations must be established, and in-vivo models of human HSC function must be optimized to better assess the functionality of putative human ESC-derived HSCs. In addition, embryonic stem-cell derived progeny often represent primitive embryonic hematopoietic cells, rather than their definitive adult counterparts; this critical issue must also be addressed.

The literature firmly establishes that it is possible to isolate HSCs and certain mature blood lineages from both mouse and human ESCs. Although several issues remain to be addressed, these data demonstrate the value of ESCs as a potential source of transplantable HSCs.