Biomedical engineers and medical researchers at the University of New South Wales (UNSW) in Australia have independently made discoveries about creating embryonic blood stem cells that could one day eliminate the need for donor blood stem cells. in the magazine ‘Cell Reports’. These …
Biomedical engineers and medical researchers at the University of New South Wales (UNSW) in Australia have independently made discoveries about creating embryonic blood stem cells that could one day eliminate the need for donor blood stem cells. in the magazine ‘Cell Reports’.
These achievements are part of the movement in regenerative medicine towards the use of “induced pluripotent stem cells” for the treatment of diseases, in which stem cells are obtained by reverse engineering from cells of adult tissues instead of using embryos. humans or live animals. In addition, they note that using the cells themselves to generate blood stem cells could eliminate the need for donor blood transfusions or stem cell transplants.
But, although we have known about induced pluripotent stem cells since 2006, scientists still have much to learn about how cell differentiation in the human body can be artificially and safely mimicked in the laboratory in order to offer a specific medical treatment.
Two studies by UNSW researchers in this field shed new light not only on how blood stem cell precursors are produced in animals and humans, but also on how they can be artificially induced.
In their study, researchers from the UNSW School of Biomedical Engineering demonstrated how a simulation of an embryo’s beating heart using a microfluidic device in the laboratory led to the development of “precursors” of human blood stem cells, which are stem cells about to become blood stem cells.
And in a paper recently published in Nature Cell Biology, UNSW Medicine & Health researchers revealed the identity of cells from mouse embryos responsible for creating blood stem cells.
Both studies are important 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 patientsamong others, who have been subjected to high doses of radio and chemotherapy, to replenish their depleted blood stem cells.
In the Cell Report study, the main authorthe doctor Jingjing Liand other researchers described how a 3-cm by 3-cm microfluidic system pumped blood stem cells produced from an embryonic stem cell line to mimic an embryo’s heartbeat and blood circulation conditions.
They point out that in recent decades, biomedical engineers have tried to make blood stem cells in laboratory dishes to solve the problem of a shortage of donor blood stem cells, but no one has yet been able to pull it off.
“Part of the problem is that we do not yet fully understand the processes that take place in the microenvironment during embryonic development and that lead to the creation of blood stem cells around day 32 of embryonic development. –explains Dr. Li–. So we made a device that mimics heartbeat and blood circulation and an orbital shaking system that causes shear stress. -or friction- of blood cells as they move through the device or around in a dish“.
These systems fostered the development of precursor blood stem cells that can differentiate into various blood components.: white blood cells, red blood cells, platelets and others, and verified that this same process, known as hematopoiesis, was reproduced in the device.
The study co-authorassociate professor Robert Nordonadmits he was amazed that the device not only created blood stem cell precursors that went on to produce differentiated blood cells, but also created the tissue cells of the embryonic heart environment that is crucial to this process.
“What surprises me about this is that blood stem cells, when they form in the embryo, they form in the wall of the main vessel called the aorta —continue–. And they basically come out of this aorta and go into the circulation, and then they go to the liver and form what’s called definitive hematopoiesis, or definitive blood formation.“.
He adds that “getting an aorta to form and actually getting the cells out of that aorta into the circulation, that’s the crucial step needed to generate these cells“.
“What we’ve shown is that we can generate a cell that can make all the different types of blood cells —highlights–. We have also shown that it is closely related to the cells lining the aorta. -as far as we know its origin is correct– and that proliferates“.
The researchers are cautiously optimistic about their success in emulating the heart conditions of embryos with a mechanical device. They hope it can be a step toward solving the problems that currently limit regenerative medical treatments: the shortage of donor blood stem cells, the rejection of donor tissue cells, and the ethical issues surrounding the use of embryos. of IVF.
“Blood stem cells used in transplants require donors with the same tissue type as the patient Professor Nordon recalls. Making blood stem cells from pluripotent stem cell lines would solve this problem without the need for donors with the same tissue type, providing an abundant supply to treat blood cancers or genetic diseases.“.
Dr. Li announces that they are working on expanding the manufacturing of these cells using bioreactors. In the meantime, and working independently of Dr. Li and Professor Nordon, Professor John Pimanda and the doctor Vashe Chandrakanthan from the UNSW School of Medicine and Health were investigating 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 make blood stem cells from the cells that line blood vessels, known as endothelial cells.
“This process was already known to take place in mammalian embryos, where endothelial cells lining the aorta transform into blood cells during hematopoiesis —says Professor Pimanda–, but the identity of the cells that regulate this process had until now been a mystery“.
Professor Pimanda and Dr Chandrakanthan solved this puzzle by identifying cells in the embryo that can convert embryonic and adult endothelial cells into blood cells. These cells, known as Mesp1-derived PDGFRA+ stromal cells, reside below the aorta and only surround it in a very narrow window during embryonic development. Knowing the identity of these cells provides clues as to how mammalian adult endothelial cells can be spurred to create blood stem cells, something they normally cannot do.
“Our research showed that when embryonic or adult endothelial cells mix with Mesp1-derived PDGFRA+ stromal cells, they begin to produce blood stem cells.“, he stresses.
Although more research is needed before translating this discovery into clinical practice, including confirmation of the results in human cells, the discovery could provide a potential new tool for generating graftable hematopoietic cells.