August 25th 2006.
Shinya Yamanaka and Kazutoshi Takahashi announced that they had made a huge discovery! One that would change the stem cell field and get them a Nobel Prize. They had discovered that adult cells, like your skin cells for example, could be reprogrammed to, once again, look and function like embryonic stem cells with the potential to become any cell in your body AGAIN! They had created induced pluripotent stem cells, or iPSCs for short. Before this, we believed that once a cell had started to differentiate, or become more specialised, it could never return! But this discovery had the potential to revolutionise the medical field as we know it!
What are iPSCS?
So, in a previous blog post I introduced you to the different types of stem cells which people are more familiar with – embryonic and adult stem cells. But there is another type – the induced pluripotent stem cell!
iPSCs are similar to embryonic stem cells in their features and function. So, they can keep making identical copies of themselves, called self-renewal, and they can make any cell type you can find in your body, also called pluripotent. The main difference between iPSCs and embryonic stem cells is where they have come from, and it is their origin that makes them so special!
Embryonic stem cells, as their name suggest some, come from an early stage embryo called a blastocyst. iPSCs can be made from adult cells – so the cells that are in your body right now! There are obviously lots of ethical issues and regulations surrounding the generation of embryonic stem cells, but iPSCs can overcome these issues and generate a constant supply of cells that can be used to treat so many diseases! And have the added bonus, that these cells can be personalised for you!
How do we make iPSCs?
As I’ve mentioned, iPSCs can be made from the adult cells that are in your body right now! This is usually done by taking some skin cells or blood from the patient. These cells are cultured in a dish until the reprogramming step – which is the main step that converts an adult cell back into a pluripotent cell (Reminder: embryonic stem cells are pluripotent cells, which means that they can become any cell type in the body!!). The group in Japan led by Yamanaka and Takahashi identified that there were four proteins needed to reprogram these skin cells – called the reprogramming factors. These proteins were called OCT4, SOX2, KLF4 and c-myc. These factors were added to the skin cells and eventually they became pluripotent again, and became iPSCs that were patient-specific.
What can we use iPSCs for?
So now, in my cell culture dish, I have got pluripotent iPSCs that have come from a patients skin cells. They were originally skin cells, but now they can become any cell type in the body. To do this we need to program them to make whatever cell type we want – a process called directed differentiation.
Much like when we reprogrammed the skin cells into iPSCs, directed differentiation requires treating our iPSCs with different protein factors. Which factors we use, depends on what cells we want to make. For example, to make a heart cell we might need Factor A, B and C, for a brain cell we might need Factor D, E and F and for a muscle cell we might need Factor A, D and G.
Once we have made our new cell type from our iPSCs, there are two main routes they can be used for. For this example, imagine we want to make some heart cells. Our newly differentiated patient-specific iPSCs will continue to be cultured in the lab, and new drugs can be tested on these cells to see how that particular patient could respond to these new treatments. However, for me, the more exciting use is that these patient-specific heart cells could be used for transplants. And it is not just heart disease that could benefit! There are thousands of diseases and conditions, like Parkinson’s, stroke, blindness and even cancers, that could be treated, simply, by replacing the ‘bad’ cells with these brand spanking new ones and allowing the organ to heal itself!
Usually, when we try and put new cells into a patient, their body doesn’t like it! Our body’s immune system usually kills them off before they even get a chance to try and fix the problem. But that is the beauty of iPSCs, as they are patient-specific – we would be putting the patient’s own cells back into their body, so their immune system would already be familiar with them.
For me, the therapeutic potential of iPSCs is huge!
Are we there yet? You would have thought that ten years after this remarkable discovery, we would have some treatments to show for it?
Are we there yet? That familiar phrase from all family road trips. A family camping trip starts off full of excitement for everyone. Then a few hours into that long drive, the magic slowly rubs off for the kids, even though they are lease with books and iPads full of games and films. The boredom sets in. Then, sitting in the fifth traffic jam of the day, you start to wonder if you will ever get there.
Unfortunately, waiting for stem cell discoveries to turn into actual treatments is a bit like this. But instead of the timescale being hours, it’s more like decades! But DO NOT think that nothing is being done – in fact every effort is being made to turn this discovery into treatments for a whole host of diseases and conditions.
A decade since the discovery of iPSCs and, personally, I think the true full potential of these cells has yet to be realised.
When will the dream come true?