New blood stem cell research could change the future of medicine, say scientists in Australia
Biomedical engineers and medical researchers at UNSW Sydney have independently made discoveries about embryonic blood stem cell creation that could one day eliminate the need for blood stem cell donors.
The achievements are part of a move in regenerative medicine towards the use of ‘induced pluripotent stem cells’ to treat disease. Two studies have emerged from UNSW researchers in this area that shine new light on not only how the precursors to blood stem cells occur in animals and humans, but how they may be induced artificially.
Researchers from UNSW School of Biomedical Engineering demonstrated how a simulation of an embryo’s beating heart using a microfluidic device in the lab led to the development of human blood stem cell ‘precursors’, which are stem cells on the verge of becoming blood stem cells. Meanwhile, researchers from UNSW Medicine & Health have revealed the identity of cells in mice embryos responsible for blood stem cell creation.
Both studies are significant steps towards an understanding of how, when, where and which cells are involved in the creation of blood stem cells. In the future, this knowledge could be used to help cancer patients, among others, who have undergone high doses of radio- and chemotherapy, to replenish their depleted blood stem cells.
The creation of blood stem cells
Lead author Dr Jingjing Li and fellow researchers described how a 3cm x 3cm microfluidic system pumped blood stem cells produced from an embryonic stem cell line to mimic an embryo’s beating heart and conditions of blood circulation. In the last few decades, biomedical engineers have been trying to make blood stem cells in laboratory dishes to solve the problem of donor blood stem cell shortages.
“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,” Li said.
“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.”
Study co-author Associate Professor Robert Nordon added: “The thing that just wows me about this is that blood stem cells, when they form in the embryo, form in the wall of the main vessel called the aorta. And they basically pop out of this aorta and go into the circulation, and then go to the liver and form what’s called definitive haematopoiesis, or definitive blood formation.
“Getting an aorta to form and then the cells actually emerging from that aorta into the circulation, that is the crucial step required for generating these cells.”
“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.”
Mystery solved
Meanwhile, and working independently, UNSW Medicine & Health’s Professor John Pimanda and Dr Vashe Chandrakanthan were doing their own research into how the stem cells are created in embryos.
In their study of mice, the researchers looked for the mechanism that is used naturally in mammals to make blood stem cells from the cells that line blood vessels, known as endothelial cells.
Pimenda said: “It was already known that this process takes place in mammalian embryos where endothelial cells that line the aorta change into blood cells during haematopoiesis. But the identity of the cells that regulate this process had, up until now, been a mystery.”
The puzzle was solved by identifying the cells in the embryo that can convert both embryonic and adult endothelial cells into blood cells. The cells – known as ‘Mesp1-derived PDGFRA+ stromal cells’ – reside underneath the aorta, and only surround the aorta in a very narrow window during embryonic development.
Dr Chandrakanthan stated: “Our research showed that when endothelial cells from the embryo or the adult are mixed with Mesp1-derived PDGFRA+ stromal cells, they start making blood stem 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 engraftable haematopoietic cells.
The study is published in Cell Reports.
Image: The microfluidic device that emulated an embryo’s heartbeat and blood circulation. The cell seeding channels are indicated by red food dye, while the heart ventricular contraction control channels and circulation valve control channels are indicated by blue and green food dye respectively.
Credit: Jingjing Li, UNSW Sydney
