Research keys on building stockpiles of organs

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A pig lung inflates at a university laboratory.

Dr. Zain Khalpey stands next to a ghostly white lung pumping rhythmically on the table next to him. “That’s pretty damn good, actually,” Khalpey says as he gazes at the data recorded by the lung’s ventilator.

The ventilator indicates that the pig lung is inflating and deflating like a normal lung. Experiments such as this bring research a step closer to the operating room.

Khalpey, an associate professor of surgery at the University of Arizona, focuses his research on making more organs available to patients who need a transplant. Every day, 18 people on organ transplant lists die, according to the U.S. Department of Health and Human Services.

In Arizona patients have to wait two to three years for a lung transplant, according to the U.S. National Library of Medicine. This waiting period is emotionally and financially draining for patients.

Khalpey is trying to shrink the wait time. He is taking damaged organs and refurbishing them so they end up in a needy patient’s body. Other organs too damaged to be refurbished are stripped of their cells and used to grow new organs with the patient’s stem cells.

In the future, donor organs may not even be needed. Khalpey is working on hybrid organs that are 3-D printed and then seeded with the patient’s stem cells.

From London to Tucson

Khalpey’s passion for transplant surgery started on a rainy day in 1990s London. A 16-year-old boy lay on the operating table about to undergo a heart-and-lung transplant. Cystic fibrosis caused his lungs to become a breeding ground for infection that whittled away his ability to breathe.

A team of surgeons replaced the boy’s lungs as well as his heart because he was more likely to survive with donor organs. The medical team rushed the boy’s viable heart to a second operating room, where it gave new life to another patient.

Both operations were a success—but at a cost. For the rest of their lives, both patients would need to take expensive medications that would prevent their immune system from rejecting the transplanted organs. Those lifelong medications also increased the likelihood that both patients might develop new afflictions, such as diabetes, osteoporosis, kidney damage and cancer.

A medical student in the operating room believed that transplant surgery could be improved. That medical student was Zain Khalpey.

Born in Zimbabwe, Khalpey had traveled to England to study medicine. He completed his medical degree at the University of London and a doctorate in cardiothoracic surgery, bioenergetics and cardiac transplantation at London’s Imperial College. Khalpey then trained at Harvard Medical School and the Mayo Clinic to master cardiothoracic surgery and transplant surgery. Inspired by UA’s history with artificial heart transplants, Khalpey came to Tucson in 2013.

Saving organs

Hospitals discard damaged organs every day, but recently some of these organs have found their way to Khalpey’s lab in the Medical Research Building. Khalpey investigates ways to recondition lungs so they have the potential to save lives. “Reconditioning means that you have a lung that is marginally damaged that you want to optimize,” he said.

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Dr. Zain Khalpey

Khalpey and his team preserve damaged lungs in a solution that slows the reactions going on inside the cell. The researchers then soak the lungs in a series of different solutions that reduce the damage. After the researchers test the lungs’ performance, they are ready for transplant long after their traditional expiration date.

“Every test we do (on these organs) is translatable and exactly what we’d do in the operating room,” Khalpey said.

Khalpey hopes to test this technique in the next year through a clinical trial at the University of Arizona Medical Center.

“Our new therapies will provide more long-term benefits for lung transplant recipients,” said Anthony V. Louis, a research specialist and registered respiratory therapist in the Khalpey lab. “Patients on the lung transplant wait list will be transplanted quicker than current times because of the potential increase in the number of donor lungs qualifying for donation.”

Growing with ghosts

No matter how much work Khalpey and his team do, some organs will never be suitable for reconditioning. They are, however, useful to study. In these cases, the researchers strip the organ of its cells in a process known as decellularization.

“(Decellularization) entails washing out the lung with different solutions like detergents that take out all of the cellular matter,” said Destiny Lagrand, a cardiothoracic transplant researcher and administrator in the Khalpey lab.

All that remains after the seven-hour process is the organ’s ghostly white bioskeleton. It is composed of the fibrous proteins that serve as a backbone for the organ’s cells.

Using a sterile, tightly controlled incubator called a bioreactor, Khalpey and his team are experimenting with reseeding the bioskeleton with stem cells from a patient who needs an organ. This new organ would be an instant match for the stem cell donor and would not require immunosuppressive medication after transplant.

The process is still experimental, but Khalpey is confident that it can be used in humans in the future. “(Previous efforts at reseeding) were more science fiction, and we need to bring it to reality,” he said. “Once I’m happy with reseeding and we have cellular integrity, I will put {reseeded lungs) in a pig.”

If tests in animals are successful, we may not be far off from having bioreactors in hospitals all over the world.

The reseeding process is expensive and takes more than a month of work by trained scientists. “It takes a lot of resources,” Khalpey said, “but if you think about what it could do to people who are waiting for lung transplants, then you can’t put a price on that.”

Organs fresh off the presses

Reseeding organ bioskeletons may work for simple organs such as bladders, but it has been difficult to scale up to more complicated organs such as the heart and lungs. To bridge this gap, Khalpey and his team have begun using bio-inks made of living cells in 3-D printers to create new organs, cell by cell.

“What I see happening much quicker (than reseeding) is building bioartificial organs,” Khalpey said. “This means using hybrid devices with human cells and matrices to work like a heart or a lung.”

These hybrid organs may not have to look like a traditional heart or lungs. By seamlessly melding tissue with technology, researchers could outsource some of the complicated physiological functions to machines.

Although these new hybrid organs might look strange, Khalpey believes that they are crucial to solving the organ shortage. 3-D printing has the potential to lower the cost of these custom organs and may be an easier technical problem to solve than reseeding.

“It’s not ambitious; it’s doable,” Khalpey said. “I think we can do it faster than we can reseed an organ.”

In the basement below Khalpey’s lab, the Cardiopulmonary Stem Cell Biobank contains a variety of tissues preserved in liquid nitrogen. Khalpey created this biobank after moving to Tucson because he wants to make it easier for other scientists and their students to find solutions for the organ shortage.

“I think it’s important to excite their minds,” Khalpey said. “That’s the reason why I’m in the academic environment: to share.”

Patrick O’Connor is a reporter for Arizona Sonora News, a service of the School of Journalism at the University of Arizona. Reach him at patrickoconnor@email.arizona.edu

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