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Don’t worry, bee happy: Royal jelly keeps embryonic stem cells agile

Honeybee royal jelly affects the developmental potential of mouse stem cells. A structurally similar protein in mammals could aid stem cell research.

Royal jelly — the specialized goop that honeybees use to cultivate a new queen for a hive — is legendary among elementary-school-aged science nerds. (I state this with confidence from my sample size of one.)

Somehow nurse bees cultivate royalty from lowly larvae that would normally become plain Jane worker bees simply by tweaking their diet. It's no wonder that kids and scientists alike find this developmental about-face fascinating, and wondered what other biological effects it might have.

Now dermatologist Kevin Wang, MD, PhD, and plastic and reconstructive surgeon Derrick Wan, MD, have found that the active ingredient in royal jelly (a protein called royalactin) also affects the developmental potential of mammalian stem cells. The finding, which was published in Nature Communications, is particularly interesting because royalactin is not expressed in mammals.

The unexpected finding is likely to fan the flames of a millennia-old debate as to the potential regenerative power of royal jelly, the allure of which has quivered enticingly on the cusp of alternative medicine like a renegade blob of grape jelly about to escape the confines of a sandwich. 

As I described in our release:

Embryonic stem cells are potent, but fickle. When grown in the laboratory, they often want to abandon their stem cell state and differentiate into specialized cells. Researchers have devised ways to keep the cells in line by adding molecules that inhibit differentiation to the environment in which the cells grow.

To their surprise, Wang and colleagues found that the addition of royalactin stopped the embryonic stem cells from differentiating, even in the absence of the inhibitors.

Keeping stem cells from differentiating in the laboratory is a critical step in learning how to using them for research or therapies. After all, one can't have their precious stem cells suddenly up and becoming a mishmash of other cell types.

Although mammals don't make royalactin, Wang and Wan wondered if they might make any other, structurally similar proteins. They used a database that infers the three-dimensional structure of proteins to identify NHLRC3, a mammalian protein that is produced early in embryonic development in all animals from eels to humans. Further studies showed that NHLRC3 had a similar effect as royalactin on mouse embryonic stem cells, keeping them young and developmentally agile (a state known as pluripotency). They renamed the protein Regina, which is Latin for queen.

Wang and Wan next plan to investigate whether Regina has any effect on wound healing or tissue regeneration in mammals.

As Wang said:

It’s fascinating. 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.

Photo by Jim, the Photographer

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