Honeybees may hold the secret to stem cell youth
New research uncovers some of the 'magical' properties of royal jelly.
In the complex hierarchy of the beehive, the queen bee is the sacred matriarch who keeps the colony alive and organized.
The queen bee lays the eggs from which the larvae will hatch. These larvae later become either the new workers, which are the female bees who do all the work around the hive, or the drones, the male bees whose job it is to mate with the queen.
When a queen bee dies, the colony has to ensure that a new one takes her place.
To produce a new queen bee, worker bees select the most suitable larvae and feed them royal jelly. This will allow one of them to develop into the healthy, strong, and extremely fertile adult female who then becomes the new queen bee.
Royal jelly comprises water, proteins, and sugars, but how exactly it stimulates some larvae to grow into queens rather than worker bees has remained unclear.
Still, due to its seemingly "magical" properties, many people hail this substance as a miraculous ingredient that can boost health and help maintain youth.
In a new study from the Stanford University School of Medicine in California, a team of researchers has decided to investigate how and why royal jelly might be beneficial. They have looked at its effect on one of the most promising targets of clinical research, namely mammalian stem cells. These undifferentiated cells are capable of turning into any specialized cells, serving any function.
"In folklore, royal jelly is kind of like a super-medicine, particularly in Asia and Europe, but the DNA sequence of royalactin, the active component in the jelly, is unique to honeybees. Now, we've identified a structurally similar mammalian protein that can maintain stem cell pluripotency," explains senior author Dr. Kevin Wang.
The researchers tell the story of their current findings in the journal Nature Communications.
The 'magic' ingredient of royal jelly
"I've always been interested in the control of cell size, and the honeybee is a fantastic model to study this," says Dr. Wang. "These larvae all start out the same on day zero, but end up with dramatic and lasting differences in size. How does this happen?"
In this study, Dr. Wang and his team honed in on a protein called royalactin that is present in royal jelly. They believed that this protein may be, in great measure, responsible for stimulating the impressive cell growth in the larvae that the worker bees select to become queen bees.
In order to study its effects, the researchers decided to apply royalactin to embryonic stem cells, or undifferentiated cells, that they had collected from mice.
"For royal jelly to have an effect on queen development, it has to work on early progenitor cells in the bee larvae," Dr. Wang notes. "So we decided to see what effect it had, if any, on embryonic stem cells," he adds.
Embryonic stem cells are the perfect candidate in clinical research as they have the potential to turn into any specialized cell, playing any role. This potential is called "pluripotency."
Replacing aging, damaged specialized cells with fresh ones that have grown from stem cells has, in theory, the potential to help address any number of diseases. As a result, it is important for researchers to have access to healthy, "youthful" stem cells that they can keep in the labs in their undifferentiated forms until they need to use them.
A protein named 'Regina'
However, Dr. Wang explains, stem cells soon differentiate under lab conditions and become unusable. To keep their pluripotency intact, researchers have had to devise complex inhibitors.
When they added royalactin to embryonic stem cells, the investigators found that it maintained their pluripotency for longer — specifically, for 20 generations — without the need to administer the usual inhibitors.
"This was unexpected. 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 [leukemia inhibitor factor]," Dr. Wang notes.
Still, the researchers did not understand this response. They felt that the mammalian stem cells should not have responded so well to royalactin since mammals do not produce that protein.
They then wondered if they could find a mammalian-produced protein that might match the shape of royalactin rather than its sequence and that may also serve the purpose of sustaining cell "stemness."
Sure enough, they identified a mammalian protein called NHLRC3, which, they thought, may have a structure close to that of royalactin and might serve a similar purpose. NHLRC3, explains Dr. Wang, occurs in all early animal embryos, including those of humans.
When the researchers applied this protein to mouse embryonic stem cells, they found that, like royalactin, it helped maintain their pluripotency. For this reason, the team decided to rename this protein "Regina," which means "queen" in Latin.
"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."
Dr. Kevin Wang
In the future, the researchers plan to find out whether Regina can boost wound healing and cell regeneration. They also want to look into more ways of keeping stem cells "youthful" in the laboratory.