Cell Rep: Blood stem cell research could change the future of medicine

Biomedical engineers and medical researchers at the University of New South Wales sydney have independently discovered the creation of embryonic blood stem cells that could one day eliminate the need for blood stem cell donors

These achievements are part of the evolution of regenerative medicine toward treating disease using "induced pluripotent stem cells," which are reverse-engineered from adult tissue cells rather than using living human or animal embryos

But while we've known about induced pluripotent stem cells since 2006, scientists still have a lot to learn about how to artificially and safely mimic human cell differentiation in the lab to provide targeted medical treatments

Two studies by researchers at the University of New South Wales in this area have revealed not only how precursors of blood stem cells occur in animals and humans, but also how they are artificially induced

In a study published in the Cell Report, researchers at the University of New South Wales' School of Biomedical Engineering demonstrated how to use microfluidic devices in the lab to simulate the beating of an embryo's heart, thereby developing a human blood stem cell "precursor", a type of stem cell that is about to become a blood stem cell

In a recent article published in Natural Cell Biology, researchers at the University of New South Wales' School of Medicine and Health revealed the identity of the cells responsible for producing blood stem cells in murine embryos

Both studies are important steps

Simulates the heart

In the study, the researchers described how a 3cm x 3cm microfluidic system pumped blood stem cells produced from embryonic stem cell lines to mimic the embryo's heart beat and blood circulation conditions

For decades, biomedical engineers have been trying to make blood stem cells in lab dishes to address the shortage of donor blood stem cells

"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 production of blood stem cells around the 32nd day of embryonic development.

"So we made a device that simulates heart beats and blood circulation, and an orbital vibration system that creates shear stress or friction

These systems promote the development of precursor blood stem cells and can differentiate into various blood components – white blood cells, red blood cells, platelets, etc

Associate Professor Robert Norton, co-author of the study, said he was surprised that the device not only created blood stem cell precursors, which in turn produced differentiated blood cells, but also histiocytes in the embryonic heart environment, which is critical

"What surprised me was that when blood stem cells formed in embryos, they formed on the walls of the main blood vessels called the aorta

"Allowing the aorta to form and then the cells from the aorta into the blood circulation is a critical step

"We have shown that we can produce a cell that can form all the different types of blood cells
.
We also showed that it is closely related to cells in the inner membrane of the aorta — so we know its origin is correct — and that it multiplies
.
Norton said
.

The researchers are cautiously optimistic about their achievements in mimicking the condition of an embryo's heart with a mechanical device
.
They hope this will be a step toward addressing today's challenges that limit regenerative medicine treatments: a shortage of donor hematopoietic stem cells, donor tissue cell rejection, and ethical issues surrounding the use of IVF embryos
.

"Blood stem cells for transplantation require a donor with the same tissue type as the patient," Norton said
.

"Making blood stem cells from pluripotent stem cell lines will solve this problem without requiring an adequate supply from tissue-matched donors to treat blood cancers or genetic diseases
.
"

Dr Lee added, "We are using bioreactors to scale up the production of
these cells.
"

The mystery is solved

Meanwhile, Dr.
Lee and Professor A/P are working
independently.
Norden, Professor John Pimanda and Dr Vashe Chandrakanthan from the University of New South Wales' School of Medicine and Health are conducting their own research into how blood stem cells are produced in embryos
.

In studies in mice, the researchers looked for mechanisms
by which mammals naturally utilize vascular endothelial cells to make blood stem cells.

"We already know that this process occurs in mammalian embryos, and during hematopoiesis, endothelial cells located in the aorta are transformed into blood cells," Professor Pimanda said
.

"But until now, the identity of the cells that regulate this process has been a mystery
.
"

In their paper, Professor Pimanda and Dr Chandra Kansen describe how they solved this puzzle by identifying cells in embryos that can convert embryonic and adult intracothelial cells into blood cells
.
These cells, called "mesp1-derived PDGFRA+ stromal cells," are located below the aorta and surround the aorta
only within a very narrow window during embryonic development.

Dr.
Chandrakanthan says knowing the identity of these cells provides medical researchers with clues about how adult mammalian endothelial cells are triggered to produce blood stem cells — something they usually can't do
.

"Our study shows that when embryonic or adult endothelial cells are mixed with 'PDGFRA+ stromal cells derived from Mesp1,' they begin to make blood stem cells," he said
.

While more research is needed before translating it into clinical practice — including confirming results in human cells — the discovery could provide a potential new tool
for generating transplantable hematopoietic cells.

"Using your own cells to produce blood stem cells eliminates the need
for a donor's blood transfusion or stem cell transplant.
Unlocking the mechanisms used by nature brings us one step closer to achieving this goal," professor Pimanda said
.

essay

The simulation of the embryonic cycle enhances the hematopoietic niches and the blood development of the person