Pittsburgh Post-Gazette

Pitt modeling has potential to unlock many medical mysteries

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

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 medicaladv­ances, 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.

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.”

The results of his team’s researchwe­re 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.

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.”

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.”

 ?? Mo Ebrahimkha­ni and Joshua Hislop ?? 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 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 ?? The HeX-Embryoid model showing 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 The HeX-Embryoid model showing 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 ?? Mo Ebrahimkha­ni is an associate professor of pathology and bioenginee­ring at Pitt.
Mo Ebrahimkha­ni Mo Ebrahimkha­ni 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 Pitt graduate student Joshua Hislop is a lead researcher in Mo Ebrahimkha­ni’s lab.

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