This Blood Stem Cell Research Could Change Medicine of the Future



Researchers in biomedical engineering and medicine at the University of New South Wales (UNSW) Sydney have separately uncovered new discoveries concerning the development of embryonic blood stem cells that, in the future, may do away with the requirement for blood stem cell donors.

With these developments, regenerative medicine is moving closer to using "induced pluripotent stem cells" to treat disease. Instead of employing live human or animal embryos, adult tissue cells are used to reverse engineer stem cells in this situation.

Despite the fact that induced pluripotent stem cells have been studied since 2006, there is still much that can be learned about how to safely and artificially mimic cell development in the human body in order to give focused medical treatment.

One kind of pluripotent stem cell that can be produced directly from a somatic cell is an induced pluripotent stem cell. Any biological cell other than a gamete, germ cell, gametocyte, or an undifferentiated stem cell that makes up the body of a multicellular creature is referred to as a somatic cell.

Two recent studies in this field by UNSW researchers shed fresh light on how blood stem cell precursors can be artificially produced as well as how they develop in both humans and animals.

On September 13, 2022, researchers from UNSW School of Biomedical Engineering published one report in the journal Cell Reports. They showed how the creation of human blood stem cell "precursors," or stem cells on the verge of becoming blood stem cells, was triggered by a laboratory simulation of an embryo's beating heart using a microfluidic device.

Researchers from UNSW Medicine & Health identified the cells in mouse embryos that are in charge of producing blood stem cells in another study that was just published in Nature Cell Biology.

Both discoveries represent important advances in our comprehension of the how, when, where, and which cells contribute to the production of blood stem cells. Future applications of this understanding could include restoring the blood stem cells of cancer patients who have received heavy doses of radiotherapy and chemotherapy.

In the work published in Cell Reports, main author Dr. Jingjing Li and colleagues explained how blood stem cells from from an embryonic stem cell line were pumped through a 3cm x 3cm (1.2′′ x 1.2′′) microfluidic device to replicate an embryo's beating heart and blood circulation.

According to her, biomedical engineers have been attempting to create blood stem cells in lab dishes for the last few decades in an effort to address the issue of a lack of donor blood stem cells. But nobody has yet succeeded in doing so.

The formation of blood stem cells begins around day 32 of embryonic development, but we still don't fully understand all the activities that take place in the microenvironment during this time, according to Dr. Li.                                    
We therefore created a device that simulates the beating of the heart and blood circulation along with an orbital shaking system that creates shear stress, or friction, of the blood cells as they move through the device or around in a dish.

These systems encouraged the growth of precursor blood stem cells, which can differentiate into diverse blood cells, including platelets, red blood cells, and white blood cells. They were thrilled to observe the device's recreation of the hematopoiesis process.

Associate Professor Robert Nordon, a study co-author, expressed his surprise at the discovery that the device not only produced blood stem cell precursors that later gave rise to differentiated blood cells, but also the tissue cells necessary for the environment of the developing embryonic heart, which is essential to this process.

The fact that blood stem cells develop in the aorta, the body's principal blood conduit, as an embryo simply astounded me. They essentially emerge from the aorta, enter the bloodstream, and then proceed to the liver to generate what is known as definitive hematopoiesis, or definitive blood formation.

"The critical step needed for creating these cells is getting an aorta to grow and then the cells actually exiting from that aorta into the circulation."

"What we've demonstrated is that we can create a cell that can produce every variety of blood cell. We've also demonstrated that it proliferates and is closely related to the cells lining the aorta, proving that its genesis is legitimate, according to A/Prof. Nordon.

The success of their mechanical gadget in simulating the embryonic cardiac circumstances has the researchers cautiously optimistic. They believe it could be a first step in resolving concerns including the scarcity of donor blood stem cells, the rejection of donor tissue cells, and the moral dilemmas associated with using IVF embryos.

The issue could be resolved without tissue-matched donors by producing blood stem cells from pluripotent stem cell lines, which would provide an abundant supply to cure hereditary or blood malignancies.

Researchers from UNSW Medicine & Health identified the cells in mouse embryos that are in charge of producing blood stem cells in another study that was just published in Nature Cell Biology.

Unrelated to Dr. Li and A/Prof. Nordon, Professor John Pimanda of UNSW Medicine & Health and Dr. Vashe Chandrakanthan were investigating the development of blood stem cells in embryos on their own.

In their research on mice, the scientists searched for the process that is employed inherently by mammals to produce blood stem cells from endothelium cells, which line blood arteries.

It was previously understood that hematopoiesis, the process by which endothelial cells that line the aorta transform into blood cells, occurs in mammalian embryos.

But until recently, the nature of the cells that control this process was unknown.

Prof. Pimanda and Dr. Chandrakanthan explained in their research how they were able to solve this mystery by locating the embryonic cells that have the capacity to differentiate both adult and embryonic endothelium cells into blood cells. The so-called "Mesp1-derived PDGFRA+ stromal cells" are found below the aorta and only cover it for a relatively brief period of time during embryonic development.

According to Dr. Chandrakanthan, understanding the nature of these cells will help scientists understand how to stimulate mammalian adult endothelium cells, which are incapable of producing blood stem cells ordinarily, to produce them.

According to his study, blood stem cells are produced when adult or embryonic endothelium cells are combined with "Mesp1 generated PDGFRA+ stromal cells."

Although more investigation is required, including confirmation of the findings in human cells, before this can be applied in clinical practice, the finding may offer a new method for producing engraftable hematopoietic cells.

"Stem cell transplants or donor blood transfusions may not be necessary if one can produce blood stem cells from one's own cells. We go closer to attaining this goal by unlocking mechanisms found in nature, according to Prof. Pimanda.

funding: Stafford Fox Medical Research Foundation, Novo Nordisk, Stem Cells Australia, National Health and Medical Research Council

By UNIVERSITY OF NEW SOUTH WALES 

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