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Stem cell breakthrough towards treating childhood cancers

Research News
Tuesday, October 18, 2016 - 8:45am
Scientists from the Murdoch Children's Research Institute (MCRI) are one step closer to understanding how to create blood stem cells in the laboratory to treat blood disorders and childhood cancers like leukaemia.

The breakthrough technology will first be used to examine the underlying genetic causes and investigate better treatments for these diseases.

MCRI’s cell biology researchers, led by Dr Elizabeth Ng, Professor Andrew Elefanty and Professor Ed Stanley, have overcome a major hurdle by successfully growing blood cells in the lab that are similar to those seen inside the developing embryo. As a result, they have advanced their research towards new therapies for blood diseases and cancers. The research was published today in the journal Nature Biotechnology.

The holy grail of blood stem cell researchers worldwide will be to generate blood (haematopoietic) stem cells in the lab as an alternative to bone marrow transplants, for those patients who are unable to find a suitably matched donor.

The crucial step that MCRI’s researchers have taken is to make the right cell type that will underpin future research towards this goal.

MCRI researchers make human blood cells in the lab from pluripotent stem cells, which can turn into any cell type in the body.

Pluripotent stem cells can be cultured from early human embryos (called human embryonic stem cells), or by reprogramming cells such as skin or blood (called induced pluripotent stem cells).

The problem scientists have encountered in the past when trying to create blood stem cells from pluripotent stem cells is that the cells that emerge are not the ideal kind and do not engraft when transplanted.

MCRI researchers have now found a way to create blood cells that are similar to those that develop inside the embryo and give rise to those that circulate throughout life.

“The real stem cells come from a place in the embryo where the main blood vessel, the aorta develops,” Professor Elefanty said.

“If you can make that type of blood cell, it’s like the ‘ancestor’ of the real blood stem cells involved in setting you up for life.

“The blood cells we made much more closely mimic the first real blood cells that are made inside the embryo.”

This process takes about two-and-a-half weeks in the lab, which is close to the time taken during embryonic development, he said.

The scientists used coloured genetic tags in the cell culture to track the development of the pluripotent stem cells as they turned into the desired blood cells.

The colours allowed scientists to identify the cells they wanted to study and also indicated the cells were transitioning from blood vessels to blood cells, as they should.

Prof Elefanty’s team then studied the genes expressed by the blood cells made in the laboratory and compared them to blood cells from a human embryo.

The resulting analysis showed the lab-grown and the human blood cells expressed a very similar pattern of genes. This exciting result suggested the correct type of blood cells had been made.

“By these sorts of comparisons, we think the blood cells we can develop in the laboratory are what we call pre-haematopoietic stem cells. They express the right genes and have the right markers on the cell surface,” said Dr Elizabeth Ng, the lead author of the research.

“Essentially what we were doing was trying to get the pluripotent stem cell-derived blood stem cells to turn on the right genes. That’s actually what we did.”

The cells will still need some degree of maturation in the laboratory before they would be ready to transplant, which will be the focus of the team’s ongoing research.

Dr Ng said the research results were very convincing not only because of the correct gene expression, but because blood cells emerged from some of the blood vessels that developed in the laboratory cultures, which is exactly what happens in embryonic development.  

“We think we can replicate some of this process in the laboratory, similar to what happens in the early embryo. That gives us an opportunity to study how to do this better and make those transplantable cells in future,” she said.

“It also means we can take these cells and study abnormalities in the genes which either impair the ability to make blood cells in diseases like Thalassemia, or mutations in cells which make them cancerous like in leukaemia.”

The methods used in this research will now underpin a new project to study childhood leukaemia. This research has recently been funded by a $460,000 grant from the Children’s Cancer Foundation.

Learn more about Professor Andrew Elefanty's work here: