What if you could take a damaged lung from a deceased patient, clean it up and refurbish it for someone in need of a transplant? Or what if you could print someone a brand new human lung using a 3-D bioprinter?
These are among the ambitious goals of Dr. Zain Khalpey, a University of Arizona cardiothoracic surgeon who wants to revolutionize organ transplantation.
Every day, an estimated 79 people in the United States receive organ transplants, but an average of 18 people die waiting for transplants because of a shortage of donated organs, according to the U.S. Department of Health and Human Services. At the same time, many donor organs are routinely discarded because they are deemed unsuitable for transplant.
Khalpey, who joined the UA department of surgery this spring as an associate professor and director of clinical and translational research, hopes to change that situation. He envisions a medical landscape in which fewer organ transplants are needed in the first place, and in which organs typically disposed of as medical waste can be revitalized to help save lives.
"My love has always been in transplantation because I want to make a difference, specifically in children," Khalpey said. "I kept on seeing kids have multiple operations without resolution of the key problem resulting in a morbidly poor quality of life, so I decided to come to the U.S. to do research on transplantation."
Born in Africa, Khalpey completed his medical education in the UK and studied and worked extensively throughout Europe and the United States before deciding to pursue his organ transplantation research at the UA, the birthplace of the Total Artificial Heart.
"I think there's a rich history here, and I'm just building on the shoulders of what's already been achieved but also adding a translational angle to innovative surgical research," he said. "If I were to stand on the podium in 10 years, I'd want to be known as a translational surgeon bringing novel metabolic and cellular bench-side therapies to the clinical bedside for my transplant patients."
In addition to his clinical work at The University of Arizona Medical Center, where he recently was appointed director of the internationally renowned heart transplant program and mechanical circulatory support, Khalpey is involved in numerous research activities, focused mainly in three key areas: bridge to regeneration, organ reconditioning and organogenesis, or the creation of new organs.
The first area, bridge to regeneration, focuses on reducing the number of people who require heart transplants by improving stem cell treatments for failing hearts.
In patients requiring heart transplants, mechanical devices known as ventricular assist devices often are used to keep their failing hearts functioning while they wait for donor organs. The devices act as "a bridge to transplant." Khalpey would like to use those same devices instead as "a bridge to regeneration," as he aims to regenerate failing hearts with stem cell injections.
"I would rather not put you on the list for transplant," Khalpey said. "I would rather take your fat-derived stem cells, inject them into you and try to use the device as a bridge to regenerate your heart, rather than using transplanted tissue, where you have to be on immunosuppression for the rest of your life."
To date, clinical trials involving stem cell therapies for failing hearts have had limited success. Khalpey is involved in a series of clinical trials and studies exploring ways to improve the process. Among his efforts, he's working on transforming the cells from being pluripotent – able to differentiate into essentially any part of the body – to being multipotent – tailored to differentiate into only certain areas, such as the heart.
Khalpey's second research area, organ reconditioning, focuses on increasing the pool of donor lungs for patients requiring a lung transplant by taking donor lungs that would be thrown away and making them suitable for transplant.
He is currently developing the UA's Ex Vivo Lung Program, which will explore new ways to recondition lungs from DCD (donation after cardiac death) donors, using mechanical devices and designer drugs to manipulate the metabolism of the organs and optimize them for transplantation.
This summer, the UA will serve as a national trial site for the Expand trial, comparing the survival of DCD lungs resuscitated on a mobile ex vivo circuit versus normal lungs transplanted.
In the event that an organ can't be reconditioned, Khalpey hopes it can still be put to use in his third area of research – organogenesis, which aims to grow new organs by combining an otherwise unusable donor organ with a transplant patient's own stem cells.
The idea is that a donor heart or lung could be put into detergent and decellularized so that nothing but the organ's matrix – essentially its skeleton – remains. The organ would then be seeded with the stem cells of a patient awaiting transplant and left to grow inside a special bioreactor, developed by Khalpey and his former colleagues at Harvard and Harvard Bioscience in Boston.
"A bioreactor is like a sterile, intelligent, well-controlled and monitored incubator, where one feeds and 'cooks' this organ until it reaches a point of clinical integrity ready for implantation," Khalpey said.
Khalpey and his colleagues have already used the bioreactor to successfully grow a new pig heart and lungs and they now are experimenting with human organs. The Donor Network of Arizona has pledged all the hearts and lungs it would normally throw away to help with the research efforts. With the organs that can't be reconditioned, Khalpey plans to create a "biofarm" of frozen organ cytoskeletons for use in future organogenesis research.
Khalpley also serves as director of the department of surgery's CAPTURED Biobank. His goal is to create a bank of cardiac and thoracic tissue with a stem cell directory that could be used by medical researchers worldwide. Human stem cells would be harvested during operations, with patient consent, for future use in tissue engineered heart valves, lungs and other organs.
Finally, Khalpey also is looking at the long-range possibility of creating transplantable human hearts and lungs using a 3-D bioprinter.
Three-dimensional printing, which produces three-dimensional solid objects from digital models, has been used to create things such as architectural models, jewelry and dental crowns. Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, has used the technology to engineer a lab-grown human bladder that was successfully transplanted into a patient in 2007.
Khalpey envisions doing the same thing with hearts and lungs, seeding a printed collagen or elastic organ structure with human stem cells and putting it into the bioreactor to develop.
Ultimately, Khalpey hopes his research will lead to new options for people who aren't now getting the transplants they need.
"The biggest problems right now for heart and lung transplantation are bridging the shortage of organs in the pediatric and adult arenas, increasing the donor pool and reconditioning or re-transplanting organs that have worn out due to chronic rejection," he said.
"I need to not just reform transplantation, I need to revolutionize it."