How to grow a liver in a petri dish and save lives

Liver donors are extremely rare - In 2011, 5,805 liver transplants were completed in the US and that same year, 2,938 people died waiting for one. Needless to say, an area that needs attention. In a first of a kind study by Takebe et al. published in Nature this week we may be a step closer to solving this problem.

The group has used human stem cells (I'll go into how towards the end) to create what they have dubbed 'liver buds', that is basically miniature human livers (about 4mm in diameter). They have then taken these liver buds and surgically implanted them into mice. The surgically implanted buds were able to substantially prolong the life of mice with liver failure! This is itself is a pretty amazing feat of science! Taking some human cells, growing a mini liver, throwing into an animal with liver failure and they live longer!

The liver buds not only prolonged the lives of these mice but incorporated themselves with the mouses blood system and continued to grow after the implantation. The buds took on many features of a fully-functional liver such as producing and sending out liver-specific proteins and signals. The figure below shows the implanted bud (in the dotted area) gaining blood vessels over time (shown by the increase in red in the dotted area).

Figure showing vascularization of liver buds (reproduced from Takebe et al. (2013))

These mini livers were the result of combining 3 types of human stem cell. First, pluripotent stem cells were converted into cells that are programmed to express liver specific genes (this is done by given the cells signals that trick them into thinking they're growing in a liver). Next, they combined these liver-specific cells with some endothelial cells (the kind of cells that make your blood vessels) and some mesenchymal stem cells (these can make bone, cartilage and fat). Over time, these groups of cells interacted and self-organized into the liver buds seen above. Below is an illustration of the process of creating the liver buds (panel A) but also a visualization of them forming over time (panel B). You can see how they start as a large smear and as time progresses they come together in an organized fashion.

Figure showing A) An illustration of the methodology of the experiment and B) showing the formation of the liver buds over time. (Reproduced from Takebe et al. (2013))

The figure below is what is called a "survival curve" which illustrates the rate of death of the mice in different conditions. Every vertical drop in the line is a mouse (or mice) dying. So a flat line means the group is surviving, a rapidly decreasing line shows they a dying.

There are only two lines you need to worry about. The dotted line at the very bottom is the group of mice that had the procedure done but didn't have a bud implanted (the control group), and the solid black line at the top is the group of mice that had the procedure done and did have the liver bud implanted.

Survival curve (reproduced from Takebe et al. (2013))

This shows that when the mice don't have the treatment, over a 30-day period, they die fairly rapidly. However, when they receive the bud implants, over the 30-day period, only ONE mouse died!

I don't know about you but I find that pretty amazing and VERY exciting. Of course as with most first of a kind studies, it needs to be replicated and further studies done but the implications this has for not only those with liver damage, but with any organ damage is huge and every exciting.

PS. For those of you who do not belong to an institution and cannot view the original article there is a summary here.