Blood production (red) is visible in two-week-old haematoids. Foto: Jitesh Neupane, University of Cambridge
An organoid-like structure resembling an early human embryo has been shown to produce blood stem cells in the laboratory.
It is possible to create an embryo-like structure from human stem cells that produces blood stem cells. This is demonstrated by a study led by the University of Cambridge, published in Cell Reports on 13 October. These miniature blood factories offer insight into early development, and may in time prove useful for transplantation or other clinical purposes.
Blood production
Producing blood stem cells in the laboratory had already been achieved before, but the new organoid-like structures allow this to happen in a more natural way. Under the right culture conditions, the British researchers were able to get human stem cells to self-organise into three layers within two days. These layers – ectoderm, mesoderm and endoderm – form the basis of the body plan in a young embryo. After eight days, beating cardiac cells emerge within the structure, and after thirteen days blood production begins. Red spots become visible to the naked eye. The addition of various growth factors and cytokines, as was previously standard practice, is not required for this. It did prove necessary, however, to block growth factor TGF-β1 for correct development. Although the structures – which the researchers have named haematoids – broadly follow the development of a human embryo, they will never grow into fully formed embryos. Several essential tissues are absent for that. The haematoids develop into a structure comparable in developmental stage to a four- to five-week-old human embryo.
Differentiation
Haematoids therefore represent a good model for early organ development, the researchers claim. In addition to blood stem cells, cardiac muscle cells, skin cells and liver cells also arise. The blood stem cells in question function well and are capable of differentiating into various types of blood cell. This is demonstrated by a follow-up experiment in which the researchers cultured the haematoids in co-culture with epithelial organoids. Within ten days, the blood stem cells develop into both bone marrow and lymphoid cells, including specialised T cells. This may in future open up possibilities for patients who require such cells. By generating stem cells from, for example, skin cells, it would be possible to develop haematoids that produce the patient’s own blood cells.