Breakthrough means patient specific stem cells

Scientists in the US have created blood-forming stem cells from patients’ own cells, moving a step closer to being able to produce all types of blood cells to treat disease.

The cells that were produced from the pluripotent stem cells were a mixture of blood stem and progenitor cells, able to generate multiple human blood types when infused into mice.

Dr Ryohichi Sugimura, from Boston’s Children Hospital and first author of the study published in Nature, said: “This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells. This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions.”

Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, unsuccessfully, to use them to make blood-forming stem cells. Sugimura and colleagues exposed human pluripotent cells – both ES and induced pluripotent stem cells – to chemical signals in an effort to make them differentiate into specialised cells. This step generated hemogenic endothelium, an early embryonic tissue that eventually becomes blood stem cells – the first time this had been achieved in vitro.

The team then added transcription factors to induce the endothelium into a blood-forming state. After starting with almost 30 transcription factors, this was whittled down to five – RUNX1, ERG, LCOR, HOXA5 and HOXA9 – that were necessary for this purpose. These factors were introduced to the endothelium using lentiviruses, commonly used in gene therapy. These endothelial cells were then transferred into mice.

A number of weeks later, the mice were carrying multiple types of human blood cells in their bone marrow and blood circulation. These consisted of red blood cell precursors, myeloid cells – precursors of monocytes, macrophages, neutrophils, platelets – and lymphocytes. Some mice even mounted a human immune response after vaccination.

Dr George Daley, who heads a research lab at the Hospital, said: “We're now able to model human blood function in so-called 'humanised’ mice. This is a major step forward for our ability to investigate genetic blood disease.”