Building a human research tumor

Angela Mortari

One of the biggest obstacles to creating new cancer therapies is the time it takes to move them from lab to person. Before any treatment becomes a reality, researchers must first show that it will be safe and effective in humans. But because cancer cells in a petri dish or in research mice don’t fully replicate cancer in a person, this can be a difficult task.  

Angela Panoskaltsis-Mortari, Ph.D., part of the U’s pediatrics faculty, is aiming to change this and thinks she may have the perfect solution. With Masonic support, she is using a powerful tool called a 3D bioprinter to produce human tumors that replicate cancer in many ways, creating new possibilities for therapies that work to reach people faster than ever.

The ideal research tumor

Recently, Mortari and her team, in collaboration with Fanben Meng, Ph.D., and Mike McAlpine, Ph.D., from the College of Science and Engineering, made headlines when they became the first to use a 3D bioprinter to print living, vascularized tumors that can be studied outside the human body.

The tumors, printed entirely with human cells, not only replicated the physical structure of tumors found in people, but also included the blood vessels and other cells inside a tumor that play a key role in the spread of cancer.

Now, with Masonic support, Mortari and her team are setting out to put this powerful new research tool to use. Their study will look at whether a cancer immunotherapy being developed by U colleague Dan Vallera, Ph.D., can eliminate the blood vessels in bioprinted brain and sarcoma tumors, while keeping healthy blood vessels outside of the tumor intact.

Blood vessels are an important target because they help feed the tumor and contribute to metastasis by transporting cancer cells that have broken away from a tumor to other parts of the body. Vallera and Mortari believe that because their immunotherapy targets a protein found in high abundance on tumor blood vessels, it will destroy those vessels while sparing normal ones. If the therapy works, their next big step will be to test it in bioprinted tumors made from patients’ own cancer cells.

“We’re excited about the possibilities this research holds,” says Mortari. “Our bioprinted tumors are much more similar to what we find in the human body. Using this tool to screen potential new cancer drugs will lead to results that are more meaningful and predictive of how the drugs will impact people.”

On the leading edge of medicine, 3D bioprinting

3D bioprinting uses sophisticated software, special gels, and biological ink to print living tissues and organs on demand. While the technology is still experimental, many believe it will one day be used for organ transplants, tissue engineering, reconstructive surgeries, and more.

Mortari was introduced to 3D bioprinting while looking at ways to repair lung damage caused by graft-versus-host-disease, a serious complication that can occur after a blood and marrow transplant. Her team at the U was the first in the world to create intact, lung scaffolds in the lab by removing all the cells from the lungs of dead mice and pigs and infusing those lungs with healthy cells derived from stem cells.

“As I was reading the tissue engineering literature, I came across 3D bioprinting and wondered why we weren’t doing it here at the U,” she says. “We had all the expertise, but at the time it was so new that no one was trying it.”

So Mortari worked diligently to acquire one of the world’s first user-friendly 3D bioprinters, as well as funding from the U, to launch the 3D Bioprinting Facility in 2015.

Her first major endeavor using the new bioprinter was to create an esophagus using a bioink made from decellularized pig esophagus material and human cells. The goal of the study, which was funded by the National Institutes of Health, was to create a replacement esophagus that could be transplanted into patients with esophageal cancer.

A crucial step in making the esophagus whole was growing blood vessels in it. That’s when Mortari had another idea.

“After we successfully guided blood vessel growth in our bioink constructs, I started thinking that another powerful use for bioprinting could be the study of cancer since tumors are fed by blood vessels,” she says.

“So we got seed grants from different programs at the U and went on to create a living, vascularized tumor. And today, with Masonic funding, we are putting this tumor model to use by testing potential new cancer treatments.”

What’s next

Mortari sees a bright future for cancer research and 3D bioprinting.

After completing their immunotherapy study in bioprinted brain and sarcoma tumors, Mortari and her team plan to bioprint other tumors that can be used for testing additional therapies.

They also plan to use bioprinted tumors to fully understand how cancer cells spread.

“In addition to being an incredible tool for drug screening, one of the coolest things about this platform is that we can use it to study those cancer cells that enter the blood vessel and metastasize,” says Mortari.

The sky is the limit, and Masonic support is playing a key role in this, Mortari continues.

“This funding really gets new ideas off the ground,” she says. “It enables us to see if strategies as experimental as a printed tumor will gain traction. And ultimately, if this works for accelerating cancer research, we will see an invaluable return on investment in getting the best treatments to cancer patients safely and quickly. That’s what it’s all about.”

Angela Mortari sidebar

Nurturing new talent

In addition to leading groundbreaking research, one of the joys of working in academia for Angela Panoskaltsis-Mortari is training the next generation of scientists.

She launched the U’s 3D Bioprinting course in the College of Science and Engineering, the first course of its kind nationwide, and helped Century College in White Bear Lake, Minn., start the first bioprinting/biofabrication certificate program in the U.S.

Mortari has also mentored countless students and trainees from a diversity of disciplines, including Fanben Meng, Ph.D., a postdoctoral associate at the College of Science and Engineering who played a key role in bioprinting the world’s first living tumor with an accessible blood vessel system.  

“Not everyone fits into conventional student pathways, yet they bring perspectives and expertise that are important for solving complex problems,” says Mortari. “Bringing together students and trainees from different fields and backgrounds grows their collaborative skills and helps them understand that medical research is not a solo career. In the end, this translates into breakthroughs that would not otherwise be possible.”  

Watch Angela Mortari 3D bioprint an esophagus.

Made to Order: 3-D Bioprinting

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