The key to creating blood stem cells may lie in your blood: ScienceAlert

The key to creating blood stem cells may lie in your blood: ScienceAlert

A new study reveals that the development of stem cells in the blood depends on a protein receptor that does not sense microbes.

This discovery could open new horizons in the ongoing quest to produce blood stem cells from a person’s own blood, thus eliminating the need for bone marrow transplants.

The receptor for the protein in question, called Nod1, is already known for its role in helping to recognize bacterial infections in the body and mount an immune response, the study authors note.

But according to their research, Nod1 also appears to serve a different purpose very early in life, when the fetus’s vascular system is still developing.

The study, conducted by Raquel Espin Palazon, a geneticist at Iowa State University, suggests that this microbial sensor helps embryos force some vascular endothelial cells to turn into blood stem cells.

This could be valuable information, given its potential to shed light on how the fetus creates blood stem cells – and perhaps how we can grow these cells later in life as well.

“This will eliminate the difficult task of finding compatible donors for bone marrow transplantation and the complications that occur after a transplant, improving the lives of many patients with leukemia, lymphomas and anemia,” says Espin Palazón.

Blood stem cells are the ancestors of all the white and red cells in our blood, and produce all the components of our blood in a process called hematopoiesis.

These blood stem cells, also known as hematopoietic stem cells, originate in the body before birth, developing from endothelial cells within the fetus’s aorta.

However, while this was already clear, there were few details about what triggers this important process in the fetus.

“We know that blood stem cells are formed from endothelial cells, but the factors that cause the cell to change its identity have been mysterious,” says Espin Palazón. “We didn’t know that this receptor was needed or necessary at this early time, before blood stem cells form.”

The researchers first focused on Nod1 by analyzing public databases of human embryos, then studied the future further using zebrafish, a commonly used model organism that shares approximately 70 percent of its genome with humans.

Zebrafish embryonic blood cells
Blood cells in the zebrafish embryo. (US National Institutes of Health/Flickr)

By inhibiting or enhancing Nod1, the researchers demonstrated a positive correlation with blood stem cell formation.

To shed more light on Nod1 and blood development in humans, the study authors also collaborated with Children’s Hospital of Philadelphia, where researchers produce human induced pluripotent stem cells.

Although they are generated from the body’s adult cells, researchers have genetically reprogrammed them to mimic pluripotent stem cells – those capable of producing many different cell types – found in embryos.

Induced pluripotent stem cells can give rise to most types of blood cells, but they cannot form functional blood stem cells. However, inhibiting Nod1 caused these pluripotent stem cells to produce less blood, mirroring the effect seen in zebrafish blood stem cells.

Most of a person’s blood stem cells are located in the bone marrow, so patients with certain blood disorders often need a bone marrow transplant to provide a vital supply of blood stem cells.

But armed with this evidence about Nod1’s role in creating blood stem cells in embryos, scientists have new hope of creating a way to produce new blood stem cells from human samples, and perhaps even from the blood of patients themselves.

The researchers point out that this could help avoid not only the logistical challenges of arranging and performing bone marrow transplants, but also complications such as graft-versus-host disease, in which transplanted immune cells recognize the host as foreign and attack the recipient’s cells.

“This will be a huge advance in regenerative medicine,” says Espen Palazón.

The researchers say more research is still needed to understand not only how the body creates blood stem cells, but also when each step must occur.

“Timing is crucial. It’s as if you’re cooking and you need to add the ingredients in a certain order,” says Espen Palazon.

“My group at Iowa State University will continue to work toward a life free of blood disorders,” she adds. “I believe our investigations will pave the way for creating therapeutic blood stem cells to treat patients with blood disorders.”

The study was published in Nature Communications.

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