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Developed at Pitt, this image of a HeX-Embryoid model shows early blood cells (green) that have formed inside of blood vessels (red) surrounded by yolk sac mesoderm cells (blue) that support these tissues.
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Pitt modeling shows potential to unlock many medical mysteries

Mo Ebrahimkhani and Joshua Hislop

Pitt modeling shows potential to unlock many medical mysteries

Developed in Mo Ebrahimkhani’s lab at the Pitt Medical School, the model reverse-engineers human cells — such as from skin — into stem cells

Non-controversial advances in stem cell research that show promise to unlock many medical mysteries are happening just miles away.

Stem cell research has led to numerous scientific and medical advances, providing tools for learning about genetic disorders and diseases, studying the biological factors contributing to recurrent miscarriages, and providing tissues for healing. But despite its potential for helping medicine, it has become marred in ethical controversy because, until recently, it required the use of cells from developing embryos. That has led scientists to seek alternative options.

Researchers in Mo Ebrahimkhani’s lab at the University of Pittsburgh Medical School have done just that, taking adult specialized cells, such as easily obtained skin cells, and reprograming them to behave like stem cells.

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Unlike other embryo studies that face ethical and technical challenges, Ebrahimkhani’s model — dubbed HeX-Embryoids — mimics key aspects of embryonic development, including the formation of blood cells, offering a tool for advancing scientific research without using human fetal tissue.

“Our model,” explained Ebrahamkhani, “could help us solve the mystery of why about 60% of pregnancies fail — frequently before the mother even knows she is pregnant — allowing us to focus on the earliest stages of life that are very much hidden from our access because of technical and ethical reasons.”

Mo Ebrahimkhani is an associate professor of pathology and bioengineering at Pitt.Mo Ebrahimkhani, of the Pittsburgh Liver Research Center, is an associate professor of pathology and bioengineering at Pitt.(Mo Ebrahimkhani)

The results of his team’s research were published late last year in Nature.

Ebrahimkhani’s is not the only recently developed model using adult cells that have been reverse-engineered into stem cells — there are a few others — but his model has advantages over the others.

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The HeX-Embryoids model creates significantly more blood cells than other models. The “He” in the name refers to hematopoiesis, which is the term for blood cell formation, not just red blood cells, but white blood cells and blood clotting platelets.

“Knowing how blood is formed at its early stages of development,” Ebrahimkhani said, “opens new opportunities for understanding childhood diseases.”

By studying this process in vitro — outside of the living organism — they expect to make significant medical advances in diagnostics and establish a basis for many new treatments.

Other applications of this pioneering model extend beyond understanding childhood blood diseases. Future steps may result in the ability to scale up blood production for blood transfusions. Creating blood from one’s own body cells would be game-changing for many medical procedures.

Another exciting application of Ebrahimkhani’s work in the rapidly expanding field of personalized medicine extends beyond individualized blood cell production. Joshua Hislop, one of the lead researchers in the lab, explained the role their model can play in this burgeoning field: “We can take the cells from a person with a disease … and see what drugs they might respond poorly to and what treatments they might respond well to.”

The entire process is remarkably speedy as well. Growing individual cells into tissues that can be used for drug testing can happen in as quickly as a few weeks.

Personalized medicine applications are not limited to drug testing: Ebrahimkhani is excited about someday harvesting a person’s skin cells and using them to produce tissues beyond blood to treat diseases.

“This is [possible],” Ebrahimkhani said, “for blood diseases like cancer, for cell therapy in neurodegenerative diseases, and as a source of hepatic cells for liver disease.”

Pitt graduate student Joshua Hislop is a lead researcher in the lab.Pitt graduate student Joshua Hislop is a lead researcher in the lab.(Mo Ebrahimkhani)

And, Hislop noted, this model “is just supremely efficient.”

Because it is easy to ship to other labs and the protocol is relatively simple, he believes it will be far easier to use HeX embryoids than other models that require several more steps — allowing labs everywhere to explore this crucial stage of development as well as the other applications.

“All you have to do,” Hislop explained, “is mix these two [easily accessible] cell types at the right ratio, turn the system on, and, with almost no perturbation from us other than feeding them, you will begin to see the stages of development.”

It's important to note here that these tissues do not have the ability to become fully formed embryos and could never be implanted to create a human.

“We can use these cells,” Hislop said, “to see what we can learn to make medicine better, make ourselves better, develop new technologies, and all without ever approaching the point of trying to make an embryo.”

Roberta McLain (bmclain@govsacademy.org) is a freelance writer based in Boston.

First Published: February 16, 2024, 10:30 a.m.
Updated: February 17, 2024, 12:30 a.m.

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Developed at Pitt, this image of a HeX-Embryoid model shows early blood cells (green) that have formed inside of blood vessels (red) surrounded by yolk sac mesoderm cells (blue) that support these tissues.  (Mo Ebrahimkhani and Joshua Hislop)
Mo Ebrahimkhani, of the Pittsburgh Liver Research Center, is an associate professor of pathology and bioengineering at Pitt.  (Mo Ebrahimkhani)
Pitt graduate student Joshua Hislop is a lead researcher in Mo Ebrahimkhani's lab.  (Mo Ebrahimkhani)
This top-down view of the circular HeX-Embryoid model shows the interface of engineered induced pluripotent stem cells (iPSCs) forming the green outer layer and non-engineered iPSCs forming the inner layer where processes that mimic early embryonic organization will occur. The cells surrounding this circular area are similar to the embryonic yolk sac.  (Mo Ebrahimkhani and Joshua Hislop)
Mo Ebrahimkhani and Joshua Hislop
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