How to Turn 3D Mini-Organs into Practical Medicine

by Nick Miller

Aaron Zorn, PhD and James Wells, PhD.

Aaron Zorn, PhD, (left) directs the new Center for Stem Cell and Organoid Medicine at Cincinnati Children’s. The center is expanding upon research breakthroughs led by developmental biologist James Wells, PhD, (right) and a growing team of experts.

A critically ill baby waits too long for a liver transplant as a life slips away. A doctor needs to learn why a promising teen athlete develops a complex and debilitating intestinal disease. A drug company wants to know if its new wonder pill is safe and effective before testing it on people.

Ten years ago, solutions to these problems seemed unreachable. Now, scientists at the Center for Stem Cell and Organoid Medicine at Cincinnati Children’s are making a concerted effort to offer the world a new technology—one on the verge of helping the baby live, showing the doctor how the young athlete got sick, and telling pharmaceutical researchers whether a new drug is safe or toxic to living human tissues grown in lab.

Human organoid technology boils down to the ability to bioengineer genetically matched, three-dimensional organ tissues from a person’s own cells. It’s a technology that pundits would call “transformative” or “disruptive.”

Organoids are helping push medical science into a new era of personalized regenerative medicine, according to Aaron Zorn, PhD, a developmental biologist and Executive Director of the new organoid center. But to realize that potential, the technology must make the often-unsuccessful transition from the laboratory bench to the real world of patient care.

“I think the biggest advances and opportunities in the short term are going to come from understanding the basic biological mechanisms of how a disease progresses so we can find novel therapies and use organoids for drug screening. A decade ago the idea of growing working human tissues in a lab was still a fantasy. Now it’s a reality, so things move quickly,” Zorn says.

At Cincinnati Children’s Innovation Ventures—the medical center’s renamed and expanded technology commercialization arm—organoids reside in a category called Biologic, Cell and Tissue Therapies. The category includes tissue engineering projects such as organoid development, but also gene correction therapies for conditions such as sickle cell anemia, and vaccine innovation.

Bridging the Academic Biotech Gap

Organoids.

Tiny organoids growing in the lab have enormous potential to study disease and new medicines in fully functional human tissues without putting patients at risk.

As challenging as the science behind human organoids and gene therapy can be, overcoming financial and infrastructure limitations inherent to non-profit academic research are equally daunting. This gap between moving a promising new technology from the lab to patients is known among researchers as the “valley of death.”

To cross the gap, the non-profit academic world depends on private-sector expertise in many ways, from the medicinal chemistry to design and make deliverable clinical compounds to venture capital to the infrastructure for large-scale production, distribution, and marketing. This is where the team at Innovation Ventures steps in. Their job is to help busy scientists work through the business end of finding real markets for their innovations.

Innovation Ventures helps identify investors and potential industry partners, assists with forming start-up companies, and helps manage the pre-clinical red tape. So far, Cincinnati Children’s has formed more than a dozen start-ups in recent years.

Take organoids as an example, where many decisions regarding licensing to outside partners vs. launching startup companies are still being assessed. Finding the right strategy for each innovation is critical to success.

“It is very important for our team to help get these assets to a place—whether through intellectual property protection or identifying experiments—that will help make technologies attractive to industry,” says Justin Levy, Director of Portfolio Management at Innovation Ventures. “From there, for-profit companies can take it on, bring their unique capabilities, and invest dollars needed to get that technology to patients who need it.”

Biologic, Cell and Tissue Therapies is such a promising category that three people are helping oversee commercialization—Levy, Portfolio Manager David Wang, and Senior Acceleration Manager Leandro Christmann. All have biotech industry backgrounds and expertise.

“Organoids are a very revolutionary technology that could fundamentally alter healthcare,” Wang explains. “It has potential for multiple applications—drug discovery, a research tool for modeling human disease, or helping replace damaged organs.”

But even a potentially game-changing technology must be developed and managed.

Non-Profit Mission vs. Profit

There is an adage in non-profit academic research and medicine: “no money, no mission.” It reflects the sometimes-delicate balancing act of commercial collaborations that advance the medical center’s non-profit mission.

Zorn and the team of collaborators that make organoid technology real—in Cincinnati and around the world—started out as basic scientists. This includes James Wells, PhD, the developmental biologist who pioneered stem cell and organoid science at Cincinnati Children’s.

A decade ago when they were studying frogs and mice to unravel how bodies grow and organs form, the scientists didn’t know how their work might lead to a potentially transformative technology. But they are not necessarily surprised, either.

“I think the motivation for the basic scientist in this instance is to understand the nature of the human body, how cells work, how organs form and the basic causes of disease,” Zorn explains. “We always had the long-term vision that research in animals could be translatable to human therapy. But even as we try to commercialize and translate these discoveries, the need for basic research continues.”

Commercialization—applied the right way—can strengthen Cincinnati Children’s mission, according to Zorn.

Tangible Product on Deck

In 2016, the medical center granted a commercial license agreement to STEMCELL Technologies to make laboratory stem cell-organoid lab kits. The product may be available within two years.
The kits will provide the protocols and technology needed to allow other scientists to reprogram a person’s adult cells (like skin cells) into induced pluripotent stem cells (iPSCs), a process Cincinnati Children’s has been refining over the years.

This kind of product advances the medical center’s mission by sharing new knowledge that can improve child health, Zorn and colleagues at Innovation Ventures say.


Biologic, Cell & Tissue Therapy: Medicine Meets its Future

Inserting the correct copy of a gene into a person’s cells may help scientists grow mini-organs to determine how to treat a disease or eventually provide healthy replacement tissues. These three examples illustrate how this bold new class of therapeutic technology is making its way along the commercialization pipeline: