The simply named and intriguingly effective royal jelly is what separates queen bees from the rest. These lucky bees are selected by the colony during the larval stage and coated in the milky, nutritious substance and then go on to become large and fertile leaders of the pack. For the first time, scientists at Stanford University have not only zeroed on the protein behind these incredible growth spurts, they’ve used its structure to identify a similar protein in mammals.

Research into the royal jelly secreted by bees as led scientists to a protein in humans that keeps stem cells in their embryonic state(Credit: kostik2photo/Depositphotos)

Though it has long been known that royal jelly is the magic substance behind the rise of queen bees, scientists have been unable to determine the exact processes behind its effects. Similarly, the health benefits of royal jelly in humans also carry a lot of unknowns, but that hasn’t stopped us using it since the ancient times to try and treat all kinds of conditions, ranging from weight loss, to infertility, to skin disorders.

Determined to crack the code, scientists at Stanford University led by assistant professor of dermatology Kevin Wang turned to royalactin, a protein already suspected to be the active ingredient in royal jelly. They explored this line of thinking by applying the protein to mouse embryonic stem cells to see if they could tease out similarities in how the cells from that animal responded.

“For royal jelly to have an effect on queen development, it has to work on early progenitor cells in the bee larvae,” Wang says. “So we decided to see what effect it had, if any, on embryonic stem cells.”

With the ability to differentiate into all kinds of cells that serve specialized functions, like muscle cells, red blood cells or brain cells, embryonic stem cells have incredible potential. But growing them in the laboratory is difficult, because their natural inclination is to quickly outgrow their pluripotent state and become something else. To preserve that pluripotency, scientists must add special molecules to the culture that inhibit that behaviour.

Assistant professor of dermatology at Stanford University Kevin Wang has helped discover a protein that could…

Wang and his team found that by adding royalactin instead, they could stop the embryonic stem cells from differentiating just as well. In fact, they found that they were able to maintain the cells in their embryonic state for up to 20 generations in culture without the need for inhibitors.

“This was unexpected,” Wang said. “Normally, these embryonic stem cells are grown in the presence of an inhibitor called leukemia inhibitor factor that stops them from differentiating inappropriately in culture, but we found that royalactin blocked differentiation even in the absence of LIF.”

Further investigations revealed that the treated stem cells were activating a network of genes that coded for proteins associated with maintaining pluripotency. But they knew mammals don’t create royalactin, so what could it be? The team worked through scientific databases until they came across a protein in humans with a similar structure to royalactin called NHLRC, which is produced during embryonic development.

They then repeated their experiments on the mouse embryonic stem cells with NHLRC instead of royalactin and found it had the same effect in maintaining pluripotency, and that it triggered a similar network of genes. They promptly renamed the protein Regina, Latin for queen.

“It’s fascinating,” Wang says. “Our experiments imply Regina is an important molecule governing pluripotency and the production of progenitor cells that give rise to the tissues of the embryo. We’ve connected something mythical to something real.”

From here, Wang and his team will carry out research investigating whether Regina can have positive effects on wound healing and cell regeneration in adult animals. It could be used as another way to keep embryonic stem cells pluripotent in the lab, and could one day lead to the development of synthetic versions that deliver stocks of stem cells in the human body. And those kinds of drugs could be used for all kinds of things, from generating healthy tissue for damaged hearts, degenerating eyes, injured spinal cords and severe burns. And hey, if nothing else, the work has at least shed new light on an age-old debate.