Blood stem cells, or haematopoietic stem cells (HSCs), are a step closer to being made in the lab, thanks to methods described in two Nature papers published this week. The development could have promising implications for cell therapy, drug screening and studies of leukaemia development.
Blood cells are made from HSCs that emerge during embryonic development from specialized endothelial cells found lining the walls of blood vessels during embryonic development.
George Daley and colleagues first used chemical signals to convert human pluripotent stem cells into haemogenic endothelial cells, then coaxed them to become HSC-like by altering levels of seven key transcription factors. In a second paper, Shahin Rafii and colleagues used adult mouse endothelial cells as their starting material, then altered levels of key transcription factors to drive their transition to cells with properties of mouse HSCs.
Both groups then used environmental signals to mature the HSCs. Daley’s team transplanted human cells into the bone marrow of adult mice, and Rafii’s team grew mouse cells on a layer of fetal endothelial cells. The resulting cells had all of the hallmarks of HSCs: they could engraft into transplanted recipients and give rise to multiple different blood cell lineages.
Although the work by Rafii and colleagues focuses on mouse cells, human adult endothelial cells can readily be obtained from healthy donors, and Daley and colleagues used cells obtained from donors and reprogrammed to pluripotency. This holds promise for personalized leukaemia therapies in which HSCs derived from a patient’s own cells could potentially be used to treat the disease.
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