Blood stem cell research could revolutionize the medicine of the future

Biomedical engineers and medical researchers at the University of New South Wales (UNSW) in Australia have made independent discoveries about creating embryonic blood stem cells that could one day eliminate the need for donor blood stem cells in the journal Cell Reports. These…

Biomedical engineers and medical researchers at the University of New South Wales (UNSW) in Australia have made independent discoveries about creating embryonic blood stem cells that could one day eliminate the need for donor blood stem cells in the journal Cell Reports.

These advances are part of a movement in regenerative medicine toward the use of “induced pluripotent stem cells” to treat diseases, in which the stem cells are obtained by reverse engineering from adult tissue cells, rather than using embryos, humans or living 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 even though we’ve known about induced pluripotent stem cells since 2006, scientists still have a lot to learn about how cell differentiation in the human body can be artificially and safely mimicked in the lab to offer specific medical treatment.

Two studies by UNSW researchers in this area 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 UNSW’s School of Biomedical Engineering demonstrated how simulating the beating heart of an embryo using a microfluidic device in the laboratory led to the development of human blood stem cell ‘precursors’, which are stem cells that will become blood stem cells.

And in a paper recently published in Nature Cell Biology, UNSW Medicine & Health researchers have 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 making blood stem cells. In the future, this knowledge can be used to help cancer patientsamong others who underwent high-dose radio and chemotherapy to restore their depleted blood stem cells.

In the Cell Report study, lead authorthe doctor Jingjing Liand other researchers describe how a 3 cm by 3 cm microfluidic system pumps blood stem cells produced from an embryonic stem cell line to mimic an embryo’s heart rhythm and circulatory conditions.

They point out that in recent decades, biomedical engineers have been trying to make blood stem cells in lab dishes to solve the problem of the shortage of donor blood stem cells, but no one has yet succeeded.

Part of the problem is that we still do not fully understand the processes that occur in the microenvironment during embryonic development that lead to the creation of blood stem cells around day 32 of embryonic development. Dr. Li explains. So we made a device that mimics heart rhythm and blood circulation and an orbital shaking system that causes shear stress. -or friction- of blood cells as they move through the device or in a dish“.

These systems encouraged the development of precursor blood stem cells that could differentiate into different blood components.: white blood cells, red blood cells, platelets and more, and confirmed that this same process, known as hematopoiesis, was replicated in the device.

The co-author of the studyassociate 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 critical 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 a major vessel called the aorta —continued–. And they basically come out of that aorta and go into the circulation, and then they go into the liver and form what’s called definitive hematopoiesis or definitive blood formation.“.

He adds that “forming the aorta and actually getting the cells from that aorta into the circulation, that’s the crucial step needed to generate those cells“.

What we’ve shown is that we can generate a cell that can make all the different types of blood cells —accents–. We have also shown that it is closely associated with the cells lining the aorta. -as far as we know its origin is correct– and it multiplies“.

The researchers are cautiously optimistic about their success in emulating the cardiac conditions of embryos with a mechanical device. They hope that this could be a step towards solving the problems that currently limit regenerative medicine treatments: the shortage of donor blood stem cells, the rejection of donor tissue cells, and the ethical problems associated with the use of IVF embryos.

Blood stem cells used in transplants require donors of the same tissue type as the patient Professor Nordon remembers. Creating blood stem cells from pluripotent stem cell lines would solve this problem without requiring donors of the same tissue type, providing an abundance for treating blood cancers or genetic diseases.“.

Dr. Li announces that they are working on scaling up the production of these cells using bioreactors. Meanwhile, and working independently of Dr. Li and Professor Nordon, Prof John Pimanda and the doctor Dear Chandrakanthan from the UNSW School of Medicine and Health investigated how blood stem cells are created in embryos.

In their mouse study, the researchers looked for the mechanism that mammals naturally use to produce blood stem cells from the cells that line blood vessels, known as endothelial cells.

This process was already known to occur in mammalian embryos, where the endothelial cells lining the aorta transform into blood cells during hematopoiesis —says Professor Pimanda–, but the identity of the cells that regulate this process has 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 surround it only in a very narrow window during embryonic development. Knowing the identity of these cells provides clues about how adult mammalian endothelial cells can be stimulated to make blood stem cells, something they normally cannot do.

Our study showed that when embryonic or adult endothelial cells are mixed with Mesp1-derived PDGFRA+ stromal cells, they begin to produce blood stem cells.“, he emphasizes.

Although more research is needed before this discovery can be applied to clinical practice, including confirmation of the results in human cells, the discovery may provide a potential new tool for generating transplantable hematopoietic cells.

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