Bees are pretty cool. If you think about the number of sci-fi movies (think Alien or Independence Day for starters) that have used their hive social structure for the evil aliens, we are obviously fascinated with them. Now, in what sounds like science fiction, new research shows that the royal jelly secreted by queens may play a key role in keeping stem cells from differentiating.
Understanding Pluripotent Embryonic Stem Cells
To understand embryonic stem cells (ESCs), it’s first important to differentiate between both embryonic and mesenchymal stem cells. First, embryonic stem cells are pluripotent. This means they can differentiate into most any cell in the body (i.e., ectoderm, mesoderm, and endoderm cells types). Mesenchymal stem cells (MSCs) are adult stem cells, which are stem cells past the embryo stage. In other words, stem cells after you were no longer an embryo are adult stem cells. MSCs are multipotent, which means that they can differentiate into many specialized cell types within the mesodermal lineage, including bone cells (osteocytes), fat cells (adipocytes), cartilage cells (chondrocytes), and so on. MSCs take cues from their local environment that tell them what types of specialized cells to become.
At one time embryonic stem cells were the king of stem cell research and were being pushed as miracle cures for many diseases. A couple of things happened at once: the Bush administration banned embryonic stem cell research and mesenchymal stem cell research and treatments began to make headway and now far exceed ESC research (see stem cell research comparison graph at this link).
Despite this, ESC research is still alive and well as scientists seek ways to make stem cells retain that pluripotency status. One such new study using cultured ESCs from mice seems to have done just that with its discovery of a protein in mammals similar to one found in royal jelly in, of all places, a beehive. Why is it important that a similar protein has been found in mammals (in the case of this study, mice)? Because researchers believe it will lead to ways to create tissues that only pluripotent stem cells can accomplish.
What Is Royal Jelly?
Royal jelly is used in making new bees. It's a honeybee secretion (in fact a type of extracellular matrix) that is used in the nutrition of bee larvae in the hive, as well as adult queens. It is secreted from the glands of nurse bees and fed to all larvae in the colony. When a new queen is needed, specific larvae in the hive are selected by worker bees, and these larvae are nourished with extra amounts of royal jelly in a specially constructed queen cell until one develops into an adult queen that can lay eggs.
Interestingly, I've known physicians fascinated with royal jelly for years. It always sounded a bit hokey to me, as they sell this stuff in supplement stores and the claims have always seemed a bit out there. Despite that, there are hundreds of studies, most on the effects of royal jelly on normal and cancer cells, listed in the US National Library of Medicine.
Newly Discovered Protein May Keep Embryonic Stem Cells Pluripotent
The new study found a protein in mammals that is similar to a protein (i.e., royalactin) found in the royal jelly secreted by honeybees that is instrumental in making new queen bees. Interestingly, in the first part of the study, researchers exposed cultured embryonic stem cells from mice to the honeybee protein royalactin to analyze how the cells reacted. Cultured embryonic stem cells, without being inhibited by some means, will typically differentiate into specialized cells, but applying the royalactin (without inhibitors) kept the stem cells from differentiating and retained their embryonic state and pluripotency.
The response of the embryonic stem cells to royalactin inspired the researchers to investigate whether the mammals themselves produced a similarly structured protein. They discovered the NHLRC3 protein (i.e., the Regina protein) in mice, which is actively produced in all animals, even humans, during the early embryonic stage. When this protein was applied to cultured embryonic mouse stem cells, the cells responded similarly to those exposed to royalactin, also retaining pluripotency.
So what does keeping stem cells in their pluripotent embryonic state mean exactly? Possibly more advanced disease treatments, the ability to heal larger wounds and injuries, and more advanced regeneration of cells and tissues.
Are There Other Ways to Get Pluripotent Stem Cells?
I’ve discussed induced pluripotent stem cells on this blog before. These are normal adult cells that are genetically modified to resemble pluripotent embryonic stem cells. In essence, a normal cell is tricked into reverting back to the properties of an embryonic stem cell. So cells that aren’t naturally designed to divide forever are forced to become mass cell-producing machines, which, understandably creates genetic problems in the process. In addition, induced pluripotent stem cells have been associated with a high rate of developing aggressive tumors. Learn more about this by watching my video below:
Another pluripotent cell that I’ve covered in the past is called a MUSE cell. Multilineage-differentiating stress enduring (MUSE) cells live in adult tissues (as opposed to embryonic stem cells, which live in embryonic tissues) in the human body. They become activated only under extreme stress, hence, the “S” meaning stress in the acronym. If you see clinics advertising that they are using MUSE cell therapies, this isn’t really possible. Let me explain.
In order to isolate and activate these cells, the fat or bone marrow (where MUSE cells reside) has to endure several very harsh conditions, so harsh, in fact, that all other viable cells are destroyed. In other words, if all of your cells were dying, MUSE cells would activate to help keep you alive. You can learn more about MUSE cells in my video below:
The upshot? It's no wonder why science fiction is enamored with bees. Turns out that they can teach us real science when it comes to keeping cells undifferentiated. This may well have implications in how we one day treat real patients, but in the meantime, it only reinforces the subplot of every good scary sci-fi movie. Always go after the alien queen!