Two new pieces of research out of the University of NSW in Sydney have shone new light on how the precursors to blood stem cells occur in animals and humans, and how they may be induced artificially.
In a study published in Cell Reports, researchers demonstrated how a simulation of an embryo’s beating heart, using a microfluidic device in the lab, led to the development of human haematopoietic or blood stem cells.
A second study in Nature Cell Biology, revealed the cells in mice embryos that are responsible for blood stem cell creation within the aorta.
Both studies are significant steps towards understanding how, when, where and which cells are involved in the creation of blood stem cells, which could one day eliminate the need for blood transfusions or stem cell transplantation from donors.
What are blood stem cells?
Haematopoietic or blood stem cells are the cells that give rise to all other blood cells – from white and red blood cells to platelets and more – in a process called haematopoiesis. Haematopoietic stem cell transplants are often performed for some cancer patients, after treatment (such as chemotherapy and radiation therapy) kills the patient’s own stem cells.
Scientists have been attempting to make blood stem cells in the lab to solve the problem of donor blood stem cell shortages for the last few decades.
“Blood stem cells used in transplantation require donors with the same tissue-type as the patient,” says senior author of the Cell Reports study Robert Nordon, associate professor in the Graduate School of Biomedical Engineering.
“Manufacture of blood stem cells from pluripotent stem cell lines would solve this problem without the need for tissue-matched donors, providing a plentiful supply to treat blood cancers or genetic disease.”
Pluripotent stem cells have the capacity to produce many different types of cells, including blood stem cells, but can only be sourced from animal or human embryos. On the other hand, induced pluripotent stem cells are generated directly from somatic cells – adult cells that have already differentiated into their cell type – through genetic manipulation.
But scientists still have a lot to learn about how to do it safely in the lab.
A miniature device mimicking the human heart
Scientists already knew that endothelial cells lining the aorta in the heart change into blood stem cells in embryonic development.
“Part of the problem is that we still don’t fully understand all the processes going on in the microenvironment during embryonic development that leads to the creation of blood stem cells at about day 32 in the embryonic development,” says first author of the Cell Reports study Dr Jingjing Li, a postdoctoral fellow at the Graduate School of Biomedical Engineering.
“So we made a device mimicking the heart beating and the blood circulation and an orbital shaking system which causes shear stress – or friction – of the blood cells as they move through the device or around in a dish.”
Not only did the 3cm by 3cm microfluidic device create blood stem cell precursors that went on to undergo haematopoiesis and differentiate into different blood cells, but it also created the tissue cells of the embryonic heart environment that are crucial to this process.
“What we’ve shown is that we can generate a cell that can form all the different types of blood cells. We’ve also shown that it is very closely related to the cells lining the aorta – so we know its origin is correct – and that it proliferates,” says Nordon.
“We are working on up-scaling manufacture of these cells using bioreactors,” says Li.
How blood stem cells are created in embryos
Researchers from UNSW Medicine and Health were also doing their own research in mice to identify the cells that regulate this process.
They found that cells known as “Mesp1-derived PDGFRA+ stromal cells” can convert both embryonic and adult endothelial cells into blood cells.
While more research is needed before this can be translated into clinical practice – including confirming the results in human cells – the discovery could provide a potential new tool to generate functioning haematopoietic cells.
“Using your own cells to generate blood stem cells could eliminate the need for donor blood transfusions or stem cell transplantation. Unlocking mechanisms used by nature brings us a step closer to achieving this goal,” says co-senior author of the Nature Cell Biology paper Professor John Pimanda, from the Prince of Wales Clinical School at UNSW Sydney.