Regenerative medicine breakthroughs may hold key to cures for a host of life-threatening ailments
August 1, 2019
Nearly 114,000 people await an organ transplant each year in the United States alone. Approximately 20 die every day due to a lack of available organs.
Kiho Lee is dedicated to bettering these odds. The regenerative medicine expert is working to grow transplantable human organs. By using pigs as incubators for human hearts, kidneys, livers, and lungs, he hopes to one day save millions of lives.
Lee and a multidisciplinary team of Virginia Tech researchers were awarded $241,500 by the National Institutes of Health for pioneering work in the field of regenerative medicine. The funding is first part of a two-year $442,750 federal grant.
“Let’s say someone has cancer and we need to identify an ideal treatment,” said Lee, an assistant professor of animal and poultry sciences in the College of Agriculture and Life Sciences. “We can give the patient 100 types of drugs, but he or she may die. Or, we can take human cancer cells and grow them in a dish, but the characteristics will be different. However, if we can grow cancer cells in an animal similar to humans and then administer drugs, we can identify an ideal medication for a human patient.”
Lee’s current study focuses on embryo complementation. In what may be likened to modern-day alchemical wizardry, the researcher employs gene editing technology, the modification of DNA within a cell, to coalesce two types of embryos – those unable to manufacture germ cells with those unable to reject foreign cells. Once synthesized, the embryo is then transplanted into a surrogate swine to produce a chimeric pig, meaning an animal carrying two or more distinct genomes.
“For transplantation models, most researchers use rodents,” Lee said. “But because of their small size, there are limitations in terms of what we can grow. Using large animals, such as pigs, we can design immunodeficient animals that mimic mice, the leading models right now.”
The researcher is eager to expand his team’s capacity to test more drugs – an effort enhanced by partnerships with medical schools and clinics. Such transdisciplinary collaborations bring him and his colleagues together with medical practitioners whose patients stand to benefit from a team approach. The clinicians present Lee with an array of vexing medical issues. From there, the Virginia Tech researchers help develop targeted, novel solutions to address these illnesses. And this, the direct application of his research to help people live better, healthier lives, is what most inspires Lee.
“It’s not just basic science. I can see the practical application at clinics. It’s deeply satisfying to see our work deliver direct benefit to patients who are struggling with life-threatening illnesses.”
The NIH grant will also allow Lee and his team, including Caroline Leeth, Alan Ealy, and Michelle Rhoads, researchers in the college’s Department of Animal and Poultry Sciences, and Sherrie Clark-Deener, a researcher in the Virginia-Maryland College of Veterinary Medicine, to collaborate further on the development of organs, called organogenesis.
Three years ago, Lee made a breakthrough, one that brings the reality of successful organogenesis more sharply into focus. He developed highly unique genetically engineered pigs – pigs lacking all major lymphocytes, making them completely immunodeficient. The animals’ susceptibility to germs and disease makes them ideal candidates, something of a blank canvas, for a range of experimental treatments for diseases ranging from cancer to diabetes, not to mention human cell transplantations.
“By introducing human stem cells, we can make human tissue and transplant it back to patients,” said Lee. “We can develop organs inside of these pigs. We have done some transplantation, and we know they grow.”
Stem cell technology has reached such a level of sophistication that researchers will soon be able to generate organs that would be a perfect genetic match to their recipients. Moreover, because transplantation for human organs, take the liver for instance, does not require an entire organ, the cultivation process would require only a matter of months.
“With organogenesis, you can grow part of tissue that can be transplanted back to a patient. The functionality and potency are much better than what we can grow in a petri dish,” said Lee.
Despite the researcher’s optimism, he acknowledges that there are some differences between humans and pigs.
“We know we can transplant human cells now, though it is a very challenging process,” said Lee. “But, we are moving forward.”
The animals must be kept in an environment free of all germs and pathogens. However, Lee feels that pigs may hold the answer to successful organogenesis.
“Because my background is animal production, I want to develop a system so pigs are used as a pre-clinical model,” said Lee. “The success rate for mice is 10 percent or less. However, if you have an intermediate model such as pigs, the success rate at clinical trials increases significantly. So, I know these pig models are important. If we can at least source some studies, this will save money and time.”
In Lee’s estimation, there is no limit to the potential of this research to prescribe relief to millions of patients.
- Written by Amy Painter