Spooky science!

On this All Hallows' Eve, I've decided to spotlight one of the oddest (some would say creepy) experiments ever conducted in the biology. I hope you enjoy! Around the year 2000, researchers at Stanford were experimenting with an idea called parabiosis, which is a technical term that refers to the joining of two separate organisms into one larger organism. In the case of the Stanford lab, researchers joined the circulatory systems of two mice, one old and one young, and the results were quite extraordinary...

Figure 1: A simple schematic of how the experiment was set up!

The group, led by stem cell biologist Amy Wagers, found that when blood from younger mice was coursed through the veins of older mice, the older mice had high amounts of myelin regeneration. The myelin sheath is a material that coats the neuron and is essential for proper neuronal function. This same setup has also been shown to heal cardiac and liver tissue in aging mice. But what causes this improvement?

The same lab eventually identified a protein called GDF11 that is the probable cause of these miraculous events. When injected intravenously, GDF11 has been shown to reduce thickening of the heart, allowed for faster muscle recovery, and even increase the sense of smell in laboratory animals. It's thought that GDF11 works by increasing the activation of stem cells.

While this experiment may seem like mad science, its implications for human disease are quite large. Giving a natural protein such as GDF11 to the elderly may be safer than current drugs and do wonders in slowing down the aging process!

Okay, so the story isn't quite as scary as that of Countess Elizabeth, who was known to bathe in the blood of her victims in an attempt regain her youth. But you can't deny that's it's just a little bit spooky! Happy Halloween!

Figure 2: Happy Halloween! Love, the creepiest villain in history

Losing your vision? There's a cell for that!

I feel like I wake up every morning and experience the same few things: a hot cup of coffee, a cold bowl of cereal and an article describing some breakthrough in stem cell technology. Yesterday was certainly no different, as a paper published in the journal Lancet described an exciting study by researchers from several institutions regarding the treatment of disorders of the eye.

Figure 1: Dr. Steven Schwartz, the lead author on the above study

The scientists injected cells derived from human embryonic stem cells (hESCs) under the retina of patients in the study. These patients suffered from two diseases that lead to vision loss: age related macular degeneration and Stargardt macular dystrophy. They found that more than half of the patients improved their eyesight, which is pretty remarkable considering that it was extremely unlikely that their vision would have improved on its own. More importantly, however, was that none of the patients showed adverse reactions to the cells!

A common question I get about these therapies is as follows: if we have supplies of stem cells and if they work fairly well in animals, why aren't we using them to cure humans? The biggest roadblock for the use of stem cells in the clinic is a lack of data regarding safety. Consider this: stem cells are naturally programmed to grow into all of the cells that your body needs. As you can imagine, many scientists are concerned that reimplanting these cells into our bodies may lead to cancer, which can be loosely defined as the out of control growth of a population of cells. A robust rejection of the cells by your immune system is also a big concern!

Without a doubt, this study is an important landmark in the field of stem cell biology. Now that we've proved (at least, early on) that these cells are safe, you'll probably see many more innovative use of stem cells in human trials very soon!

Curing Diabetes, one stem cell at a time!

I've blogged about the power of stem cells before, most recently regarding their use as a potential treatment for cancer. I cannot overestimate the utility of these cells; just think, these guys can transform into any cell in the human body. That's a pretty crazy thought. Lack a particular organ or gland? We can make that for you!

Figure 1: These human stem cells were plated using a printer. Credit: Dr Will Shu / Biofabrication

As you can imagine, the therapeutic potential for research in stem cell biology is massive. I would not be surprised if the routine use of stem cells in the clinic becomes as common as an antibiotic prescription.

Case and point: Some very brilliant (and creative) researchers at the Harvard Stem Cell Institute, led by Dr. Douglas Melton were able to cure type 1 diabetes in rats using insulin-producing cells that were created from stem cells. Type 1 diabetes is a disease in which the beta cells in your pancreas, the cells that make insulin, are attacked your body's immune system. Insulin is a hormone that allows your cells to control the level of glucose in the blood, so those who suffer from diabetes have volatile blood sugar levels.

This is a massive step forward in the field, as the majority of current diabetes interventions involve patients monitoring and injecting extra insulin when necessary. Some excellent automated devices have been made to this effect, they clearly lack the advantage of using insulin produced natively in the body. Were this therapy to move into people, suffers from type 1 would no longer have to rely on any sort of injection system to deliver their insulin. Very exciting news!

As with all things, remember to take this research with a grain of salt. I don't want to sound like a debbie downer, but the jump from treating animals to people can be quite tricky. For example, researchers still need a way to ensure that any implanted cells remain unharmed by your immune system. Another challenge is the origin of the cells: the cells used in this study were derived from embryos, which remains a controversial source. Melton and his colleagues are investigating ways to generate beta cells from induced pluripotent stem cells, which is a way to make stem cells without relying on an existing embryo.

All in all, I think this story represents a win for a science and a huge leap forward for patients everywhere!

Using stem cells to treat cancer?

Cancer is a very interesting disease. As I mentioned in a previous blog post, its ability to mutate into countless different forms means that generating effective ways to combat it is no small task. Researchers and physicians usually have to be pretty creative with how they approach treatment- no one drug will help every patient! A very interesting review coming out of Nature talks about a very interesting new way in which scientists are approaching this problem. As was reported by several laboratories, it turns out that stem cells have the natural tendency to migrate towards tumors. Using this principle, biologists are beginning to hijack these stem cells to deliver a wide variety of different things. Here is a brief summary of some of the therapies discussed (for the full story, check out the paper that I linked above!

Figure 1: A colony of stem cells!

Strategy 1: Delivering Therapeutic Proteins

There are many proteins out there that can be used to cause the spontaneous death of cells. One of these proteins is called TRAIL; it binds to a protein called death receptor 4 (ominous, I know!) and causes apoptosis, which is the cells way of destroying itself. By navigating directly to the tumor, stem cells are able to deliver these noxious proteins directly to the cells they wish to kill while sparing the surrounding tissue!

Strategy 2: Stem Cell Mediated Suicide Therapy

In this treatment, stem cells migrate to the tumors of interest and convert a previously harmless drug into one that is pretty nasty! By doing, this the stem cell sacrifices itself while simultaneously preventing the risk of it going on to divide into different things. This also means that dangerous drugs will only appear at the tumor site - if the drug manages to escape and go somewhere else, it won't be toxic because it hasn't been converted any stem cells!

Strategy 3: Nanoparticle delivery

One of the biggest difficulties in getting drugs to their targets is the body's own immune system. Your innate defense system is pretty potent (which is a very good thing!), but it also means that drugs are recognized as foreign entities and are quickly destroyed. To get around this, scientist have begun to surround drugs in nanoparticles, which your body doesn't identify as being a bad thing. This "Trojan horse" method allows your therapeutic of choice to sail past the defenders and make it to the end zone. Touchdown!

Figure 2: What your stem cell friends look like delivering nanoparticles. Close enough, right?

Strategy 4: Oncolytic Virus delivery

Oncolytic viruses are viruses that selectively destroy the rapidly dividing cells characteristic of cancerous tumors. However, the delivery of such viruses is difficult due to the same hiccup described in strategy 3: avoiding host immune defenses. The ability to "hide" within a stem cell allows the virus to remain inconspicuous until the moment is right!

Figure 3: A schematic of the therapies discussed above. Pretty snazzy! Picture courtesy of Nature Reviews Cancer.

But as you may note from the the title of the review, Stem cell-based therapies for cancer treatment: separating hope from hype, not everything is as simple as it seems! The field of stem cell research is still relatively young; thus, there are still a myriad of problems with using stem cells in humans. These issues are too long to list here (contact me if you wish to discuss!), but always take any new revolutionary treatment with a grain of salt. I, however, remain incredibly optimistic that we will circumvent these challenges and that stem cell therapies will soon become routinely used in the clinic!