A team of scientists that included researchers from UGA has grown a fully functional organ from scratch in a living animal for the first time. The advance could one day aid in the development of laboratory-grown replacement organs.
The researchers created a thymus, a butterfly-shaped gland and vital component of the human immune system. Located beneath the breastbone in the upper chest, the thymus is responsible for producing T-lymphocytes, or T-cells, which help organize and lead the body’s fighting forces against threats like bacteria, viruses and even cancerous cells.
“We were all surprised by how well this works,” said Nancy Manley, a professor of genetics in UGA’s Franklin College of Arts and Sciences and co-author of the paper describing the finding in Nature Cell Biology.
“The general idea in science is that to make cells change their fate, you need to reprogram first to a stem-cell like state and then coax them to change into what you want,” said Manley, who is also director of UGA’s Developmental Biology Alliance. “But we jump-started the process just by expressing a single gene that was sufficient to initiate the entire process and orchestrate organ development.”
Researchers took cells called fibroblasts from a mouse embryo and reprogrammed them directly into a completely unrelated type of cell by increasing levels of a protein called FOXN1, which guides development of the thymus in the embryo.
When mixed with other thymus cell types and grafted onto the kidneys of genetically identical mice, these cells formed a gland with the same structure, complexity and function as a regular, healthy thymus in only four weeks.
The lab-grown thymus also was capable of producing T-cells on its own.
The research team, led by scientists from the University of Edinburgh, hopes that further refinement of their lab-made cells could form the basis of a thymus transplant for people with weakened immune systems.
“The ability to grow replacement organs from cells in the lab is one of the holy grails in regenerative medicine,” said Clare Blackburn, a professor of tissue stem cell biology at the University of Edinburgh and principal investigator for the project. “But the size and complexity of lab-grown organs has so far been limited.
“By directly reprogramming cells, we’ve managed to produce an artificial cell type that, when transplanted, can form a fully organized and functional organ,” she also said. “This is an important first step toward the goal of generating a clinically useful artificial thymus in the lab.”
Thymus disorders sometimes can be treated with infusions of extra immune cells, or transplantation of a thymus organ soon after birth, but both are limited by a lack of donors and problems matching tissue to the recipient.
While several studies have shown it is possible to produce collections of distinct cell types in a dish, such as heart or liver cells, scientists haven’t yet been able to grow a fully intact organ from cells created outside the body.
“There is still a long way to go before this could enter clinical trials or become a treatment, but it is extraordinarily exciting,” Manley said.