For the first time, researchers have grown a fully functional thymus from scratch in a living animal.
Researchers took fibroblasts from a mouse embryo and reprogrammed them directly into an 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 4 weeks.
The lab-grown thymus was also capable of producing T-cells on its own, the study showed.
The new findings appear in Nature Cell Biology.
“The ability to grow replacement organs from cells in the lab is one of the holy grails in regenerative medicine,” says Clare Blackburn, professor of tissue stem cell biology at the University of Edinburgh and principal investigator for the project, in a news release. “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 says. “This is an important first step toward the goal of generating a clinically useful artificial thymus in the lab.”
“The ability to grow replacement organs from cells in the lab is one of the holy grails in regenerative medicine.” —Clare Blackburn
Thymus disorders can sometimes 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.” —Nancy Manley, PhD
“We were all surprised by how well this works,” says Nancy Manley, PhD, professor of genetics in the University of Georgia (UGA) Franklin College of Arts and Sciences in Athens and co-author of the paper, in a news release. “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,” says 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.”
“There is still a long way to go before this could enter clinical trials or become a treatment, but it is extraordinarily exciting,” Manley says.