The popular Marvel film Deadpool, sees its antihero fight bad guys without dying because he can regenerate. Wade Wilson (aka Deadpool) has terminal cancer, and an evil set of scientists, turned this cancer into a superpower: he has accelerated healing powers as his cells can never die, continuously regenerating as cancerous cells would do. This is comic book fiction, but how far away is a regeneration reality, and are evil scientists behind it?
I have previously written about the possibility of growing new organs in my Test Tube Transplants article. However, this type of regenerative medicine is a whole different ball game. Here we investigate the possibility of growing the new body parts ourselves; this is sometimes called endogenous repair. Current research is attempting to deduce how cells cooperate to build and repair complex structures in our bodies, and how a 3D structure itself is regulated. If researchers can find out these fundamentals, we could “fix” birth defects, degenerative disease, and damage from traumatic injury to name but a few. Let’s start from the beginning; can anything already do this?
Our simple human selves already perform some regeneration. In fact, our skin cells regenerate every 2 weeks, the liver can regenerate every 300-500 days, red blood cells every 120 days, whilst bone cells are more like every 10 years. Other parts of us however never change, for example our visual cortex is set for life. Some animals could teach us a thing or two. Deer can regenerate bone (such as their antlers) each year, and a leopard gecko will regrow its tail if lost in trauma. So why don’t we regenerate this effectively? It is possible that evolution may have picked scarring over regeneration. Scarring is much quicker for repair, whilst regeneration is much more energy intensive. Mammals such as ourselves, already use/perform many energy consuming processes, which would make it difficult for us in the wild if we needed to pop off and regrow a limb.
How can we use these animals to aid our regenerative medicine dreams? Most current research uses adult salamanders (axolotls) and planarian worms, to identify any genes involved in the regeneration process, and cell to cell communications which also occur. Prof Michael Levin is leading this field of research. To regenerate, our cells must first recognise there is a damaged area before calling upon other cells (usually across the entire body) to lend a hand and fix the problem; the cells need to know what to grow and, importantly, when to stop.
Using salamanders, the researchers discovered that after a wound has sealed itself off (within hours), a group of cells migrate to the wound (i.e. a blastema). The cells have their internal clocks reset to “factory settings” so they can take the form of whichever cells are needed (e.g. brain cells for a brain). One experiment showed that when a salamander’s tail and leg were removed, and the tail subsequently grafted to where the leg should be, it turns back into a leg! In other words, the cells knew to completely alter their structure to fit with the body’s needs. On a side note, a set of tests in the ’50s showed that salamanders can’t get cancer: the salamanders would change the cancerous cells back to what they needed them to be. Incredible.
Planarian worms are also complex, with many organs and structures. If cut into 280 pieces, each piece can turn into a completely identical worm (they are thought to be immortal)! Even more intriguing is that if you train a planarian worm to respond to light and then remove its head, the regenerated head and brain can remember what it was taught. This is utterly mad, and means they are storing memory outside of the brain. Therefore, we need to understand the signals which pass between cells to unlock this process; this could lead to wearable bio-reactors.
Bio-reactors would kick-start regeneration in animals who aren’t naturally good at it (i.e. if we lost an arm etc.); we have all the information inside us, we just need something to unlock it. A simple example of this has been shown in an African frog species. The bio-reactor contained a hormone (progesterone) which promotes tissue growth, and was attached to a frog which had lost a leg; progesterone was released to the area over the next 24 hours. The frog was able to generate a structure much closer to that of a leg than that which it produced without the bio-reactor. This was a very crude and early version of what we would need for human bio-reactors, but we are a step closer.
I could talk about regenerative medicine for hours. This research is still in very early stages, with many obstacles to overcome such as our natural scarring and inflammation processes. Such work also raises new questions about ethics and what we thought we knew: what triggers the signals which determine what a cell will become in an embryo, is it electrical communication? We know it happens in the brain but it is potentially happening between all cells. We have absolutely no understanding of this bio-electric code, YET, but this could be the start of a very cool, if not a bit weird, deadpool era of medical research and innovation.