Embryonic blood stem cells could one day eliminate the need for donor stem cells for transplants. Two studies published in «Cell Reports» and «Nature Cell Biology» advance in this new regenerative medicine which is based on the use of induced pluripotent stem cells and which would serve to treat multiple diseases. The technique, he explains, relies on reverse-engineering stem cells from adult tissue cells rather than using human embryos or living animals.
The two studies by researchers at the University of New South Wales, Australia, reveal new insights not only into how blood stem cell precursors are produced in animals and humans, but also how they can be artificially induced.
The study published in “Cell Reports” demonstrates how simulating the heartbeat of an embryo using a microfluidic device in the laboratory he succeeded in developing human blood stem cell precursors, which are stem cells about to become blood stem cells.
And in the “Nature Cell Biology” paper the scientists revealed the identity of the cells in mouse embryos responsible for the creation of blood stem cells.
Both studies are significant steps toward understanding how, when, where, and which cells are involved in creating blood stem cells. In the future, this knowledge could be used to help cancer patients, among others, who have undergone high-dose radiation and chemotherapy, replenish their depleted blood stem cells.
artificial heartbeat
In the “Cell Reports” study, the authors explain how a 3 cm x 3 cm microfluidic system pumped blood stem cells produced from a lineage of embryonic stem cells to mimic an embryo’s beating heart and circulation conditions. sanguine.
For the past several decades, says study lead author Jingjing Li, biomedical engineers have been trying to produce blood stem cells in the lab to solve the problem of a shortage of donor blood stem cells. But nobody has been able to achieve it yet.
“Part of the problem is that we still don’t fully understand all the processes that occur in the microenvironment during embryonic development that lead to the creation of blood stem cells around day 32 in embryonic development,” Li says.
So the researchers made a device that mimics heartbeat and blood circulation and an orbital shaking system that causes shear stress, or friction, on blood cells as they move through the device or around a dish. .
Having an aorta form and then cells emerging from that aorta into the circulation, that’s the crucial step required to generate these cells.
These systems promoted the development of precursor blood stem cells that can differentiate into various blood components: white blood cells, red blood cells, platelets, and others. In this way they replicated this process, known as hematopoiesis, in the device.
Study co-author Robert Nordon acknowledged that he was surprised that the device not only created blood stem cell precursors that then produced differentiated blood cells, but also created the tissue cells from the environment of the embryonic heart that is crucial for this. process. «What amazes me is that blood stem cells, when they form in the embryo, they do so in the wall of the main vessel called the aorta.. And they basically come out of this aorta and into the circulation, and then they go to the liver and form what’s called definitive hematopoiesis, or definitive blood formation.”
“Getting an aorta to form and then getting cells to emerge from that aorta into the circulation, that’s the crucial step required to generate these cells,” he acknowledges.
In short, Nordon says, “what we’ve shown is that we can make a cell that can make all the different types of blood cells. And we also found that it is closely related to the cells that line the aorta, so we know its origin is correct, and that it proliferates.”
The researchers are cautiously optimistic about their success in emulating the conditions of the embryonic heart with a mechanical device. They hope it can be a step toward solving the challenges that limit regenerative medical treatments today: a shortage of donor blood stem cells, rejection of donor tissue cells, and the ethical issues surrounding the use of IVF embryos. .
Because, as this expert warns, “blood stem cells used in transplants require donors with the same type of tissue as the patient.”
Making blood stem cells from pluripotent stem cell lines would solve this problem without the need for matched tissue donors that provide a plentiful supply to treat blood cancers or genetic diseases.
On the other hand, and independently, John Pimanda and Vashe Chandrakanthan they were doing their own research on how blood stem cells are created in embryos.
In their mouse study, the researchers looked for the mechanism that is used naturally in mammals to produce blood stem cells from the cells that line blood vessels, known as endothelial cells.
The discovery could provide a new tool to generate graftable hematopoietic cells
“It was already known that this process takes place in mammalian embryos, where the endothelial cells that line the aorta are transformed into blood cells during hematopoiesis,” says Pimanda. “But the identity of the cells that regulate this process has until now been a mystery.”
In their paper, they describe how they solved this puzzle by identifying cells in the embryo that can convert embryonic and adult endothelial cells into blood cells. The cells, known as ‘PDGFRA+ Mesp1-derived stromal cells’, reside below the aorta and only surround the aorta in a very narrow window during embryonic development.
Knowing the identity of these cells, Chandrakanthan believes, provides researchers with clues as to how mammalian adult endothelial cells might be activated to create blood stem cells, something they cannot normally do.
And while more research is needed before this can be translated into clinical practice, including confirmation of the results in human cells, the discovery could provide a new tool for generating graftable hematopoietic cells.
“Using your own cells to generate blood stem cells could eliminate the need for donor blood transfusions or stem cell transplants,” adds Pimanda.