Tuesday, 21 June 2011

Everyone loves stem cells

Stem cells have been THE hot topic for a number of years now. In theory, stem cells can be turned into any other cell type and could therefore be used to repopulate a damaged organ with healthy, normal cells. Sounds cool. "Stem cell" refers to a number of different cell types, some can become any cell in the body and some can become only a small subset of cells. Bone marrow, which contains blood stem cells, has been successfully used to repopulate blood after chemotherapy since the 1950s. Half a century later, some recent papers suggest that stem cells could also be used to repopulate damaged hearts and livers, but there have also been some troubling reports about the nature of stem cells, particularly induced pluripotent stem cells.

Stem cells come in three flavours: embryonic stem cells (ES cells), induced pluripotent stem cells (iPSCs), and resident stem cells. ES cells are more of a research tool than a potential therapeutic tool. They can be used to study the normal processes which turn a stem cell into all the different cells in the body. They have their much-debated ethical pitfalls, and ES research continues to be plagued by government restrictions and the threat thereof. The advantage of ES cells is that they can be turned into literally any cell, whereas iPSCs and resident stem cells are more restricted. An iPSC cell might become a heart or liver cell, but not a brain cell. The downfall of ES cells is immune incompatibility. When foreign cells are injected into a patient, the patient's immune system will recognize them as foreign and attack them. Bone marrow and other organ donations are matched as closely as possible to the patient, but even then most patients are on immunosuppressant drugs to prevent rejection. ES cells, since the embryo is destroyed in order to get the cells, will never be genetically identical to a prospective patient and immune incompatibility will always be an issue.

iPSCs, on the other hand, are made from the patient's own cells so shouldn't be rejected. Cells taken from a person's skin (for example) are grown in dishes and turned into iPSCs through a variety of different protocols including genetic modification or drug treatment. Recently, cells from a mouse's tail have been turned into iPSCs and used to repopulate its damaged liver. iPSCs have their own problems: most iPSCs have multiple, large mutations. Putting mutant cells into someone is not exactly the best idea; not only would they be unlikely to work properly they'd also potentially form cancers. The second major problem is that iPSCs are also rejected by the host's immune system. This was quite unexpected, since iPSCs are theoretically genetically identical to their host. Changes to the cells that occur during their transformation into iPSCs seem to be recognized by the immune system, and the iPSCs are rejected. So the iPSC field now has two enormous hurdles to overcome; they must find cells that are both genetically stable and not rejected by the host's immune system. The two might have a similar solution but iPSCs are a long way from the clinic. The tail-becoming-liver experiment is still promising, but it used genetic modification with some nasty genes in order to perform its feat.  No tumours were found in the mice after 2 months, but the long-term effects remain to be determined.

Resident stem cells are perhaps the best prospect for stem cell therapies. Many of our organs have the capacity to regenerate themselves, at least partially. A person can have a big chunk of their liver removed and the resident stem cells will help it to grow back.  Bone marrow repopulates blood. Resident stem cells are specific to each organ but are already present in the body. The question is how to get them to grow when needed. Livers and blood regenerate themselves without needing to be stimulated, hearts and brains don't. Interestingly, a recent paper shows that resident stem cells in the mouse heart can grow and repopulate a damaged heart when the mouse is injected with a growth factor cocktail. The key to using resident stem cells will be finding the right cocktail for each organ. Some organs may not have stem cell populations that are inducible. It will take a lot of trial and error to find the right mix. The possibility of stimulating a population that's already in place is attractive since it circumvents the problems that arise when the cells are grown outside the body or genetically modified. Repopulating an organ from resident stem cells is a new idea and there will undoubtedly be problems along the way. Therapeutically it could only be used with partially damaged organs, since organs which are heavily damaged or removed completely wouldn't have the necessary stem cells. Some organs may not have resident stem cell populations, or those populations may not respond to growth cocktails. Neurons, for example, are particularly difficult to make. Things that work in mice don't always work in humans. And of course putting molecules into a human which stimulate growth could theoretically cause other inappropriate growth related diseases (ie cancers).

Few topics in biology have been as over-hyped as stem cells. They are a potentially powerful tool. Let's see what resident stem cell researchers come up with in the next few years.

Sunday, 5 June 2011

Sorry, it's been a while...

Yes, it's been almost a month since my last post. And I have to make one small correction- there was technically a meltdown at the Fukushima Daiichi plant. But I still stand by what I said.

I'm going to do a bit of recycling right now, so here's a little tidbit on oil droplets  I wrote about a year ago. I thought you might find it interesting. For some more of my thoughts over the last month, check out:


In the meantime, enjoy this bit about oil drops.

Like lipids through a maze

Oil droplets may be used to solve complex network problems (from 05.06.10)

The maze is a long-standing test of problem-solving and learning skills. From rats looking for cheese to children running through a labyrinth, finding the end usually requires a trial and error approach. The successful maze solver must correct a few wrong turns along the way, staying focused enough on the end goal to not get disoriented and distracted licking one’s own paws.
Now it seems that lipid droplets laced with acid have moved into the ranks of successful maze navigators. Bartosz Grzybowski and colleagues at Northwestern University found that lipid droplets can successfully navigate mazes, and can even turn back when they encounter dead ends. In this case the “cheese” is an acid which diffuses through the maze to create a pH gradient. Since the laced droplets themselves slowly release acid, the side of the droplet facing the exit becomes more acidic while the side facing the start of the maze becomes more basic. This difference in acidity creates surface tension on the droplet, which propels the droplet towards the finish line.
Two types of acid-laced droplets were used, based either on mineral oil or on dichloromethane, an organic solvent. Dichloromethane releases the acid faster than mineral oil, and the two lipids displayed different properties. The mineral oil always chose the shortest possible route. More interestingly, the faster-moving dichloromethane behaved like a cab driver encountering unexpected roadworks; it didn’t always choose the shortest route but was able to correct itself when it found a dead end. In some situations this required the droplet to backtrack for a period of time before resuming its path. When two droplets were simultaneously introduced into the maze, they rarely got in each other’s way.
This system could be useful in a number of ways. On a practical level, the movement of acid-laced droplets could be used as a micropump in equipment such as medical diagnostic tools or DNA microchips. If the system is scalable, the maze could also be used to solve more complex network problems. Tracing the paths of different droplets attracted to different targets may serve as a model for the flow of traffic through roads or websites. Robotics and plant and facility layouts could also be modeled using oil drops. The dichloromethane drop’s ability to correct errors could show what happens when slower-moving regions are introduced into the system. At what point will the drop change from a slower but more direct route to a longer but faster route?
There are two types of maze-solving experiments, testing spatial navigation or learning respectively. The oil drop experiment examines spatial navigation, where the maze-runner has no previous knowledge of the maze. To examine learning, the maze runner is placed in the same maze repeatedly; the time needed to complete the maze decreases as the runner learns. Lipid droplets can navigate, but living organisms still seem to have the edge on learning.