Bloody good: scientists create first artificial blood stem cells
A way to create replacement stem cells that can produce blood and immune cells has been demonstrated for the first time by two research teams in America.
Bone marrow transplants save thousands of lives every year in patients suffering from leukaemias and other blood disorders. But, at the moment, the only source of replacement marrow is a donor human, meaning that healthy, suitable tissue is often in short supply.
Achieving a close genetic "match", which is essential for preventing problems like graft-versus-host disease (GVHD), can also limit the pool of suitable donors.
Now two research groups in the US have published the first example of a technique that can make bone marrow stem cells from a patient's own tissues, offering doctors a way to overcome many of the present obstacles in future.
The papers describing the breakthrough, which were published this week in the journal Nature, are by Weill Cornell Medical College, New York, scientist Raphael Lis and his colleagues, and a team at the Dana-Faber Cancer Institute in Boston led by George Daley. Both achieve similar outcomes but use slightly different routes to get there.
Daley's team describe taking adult human skin and other cells and first reprogramming them into unspecialised - so-called "induced pluripotent" - stem cells. These were first briefly cultured to convert them into what are known as "haemogenic endothelial cells" which line lood vessels in a developing foetus and are capable of producing blood cells.
The team then added a cocktail of seven signalling or "transcription" factors and injected their cells into the bone marrow of mice. In this environment, the cells matured into fully fledged bone marrow stem cells capable of producing all of the normal blood elements found in a healthy human.
The other research group took a different, more efficient tack. Starting with the adult endothelial cells that line blood vessels, they added four transcription factors and cultured the cells over a 28 day period in a dish on a bed of blood-vessel lining cells to mimic the embryonic environment in which bone marrow stem cells would normally be "born" in a foetus.
The resulting cells could be injected into recipient mice that were devoid of their own bone marrow and take over producing of blood and immune cells. Moreover, the recipient animals remained healthy afterwards for their normal expected lifespans of 1.5 years. Critically, there was no sign of malignancy, which is always a concern when stem cells have been manipulated in this way.
The team also measured the constellation of genes that were switched on in their replacement bone marrow stem cells and found them to be broadly the same as normal bone marrow cells. Together, these two exciting studies show that scientists are extremely close to realising the goal of producing bone marrow stem cells from a patient's own tissue.
However, the work is still in its infancy and many questions remain to be answered about the practicality and safety of the procedure. In an accompanying review published along the two studies, Cambridge stem cell biologists Carolina Guibentif and Berthold Gottgens ask why the numbers of cells that are successfully produced by the process is very low, and they highlight the risks of the procedure used by the two US teams, which involves infecting them with a virus to introduce the reprogramming "transcription" factors into their cells. That said, it's early days...