In 2016 the UK reached a milestone of 50,000 people being alive due to the donation and successful transplantation of an organ. 4,753 organ transplantation procedures were undertaken in the UK in 2016 alone. However, there were still ~10,000 people on the transplant waiting lists in March last year, and ~1,200 people died as a result of long waiting lists last year. With transplant waiting lists so long and willing donor numbers low, how can research help alleviate the problem?
You can recieve 13 different types of transplant ranging from blood, to skin, to hearts, they’re all just as difficult to come by. In this article we’ll discuss heart transplants but be aware that research is conducted into each of the 13 areas of transplantation. The NHS Blood and Transplant research and development page discusses the areas of research under investigation in the NHS at the moment.
One type of heart transplant doesn’t rely on humans to donate, instead it uses a bovine or porcine transplant (i.e. pig or cow). The whole heart is not transplanted (although a pig’s heart is roughly the same size and strength as our own, making it a good match) but instead just a valve (e.g. aortic valve) of the heart, which is key to ensuring blood is pumped the right way around the body. Artificial valves are also produced for this procedure from materials compatible with the body using 3D printers, but patients receiving these have to take blood thinning drugs throughout their lives (i.e. anticoagulants) as blood clots are much more likely with this type of replacement. But what happens when the whole heart needs replacing?
When replacing an entire organ it must come from someone who matches your own. This match is based on three test: blood tests, crossmatch and HLA (human leukocyte antigen) testing. First, your blood types must match which is why parents may not always be able to donate to you or vice versa as your blood types may not match. The HLA test is usually only matched between people directly related as these are the antigens (i.e. induce an immune responses) we inherit from our parents. In the small off chance that you match your donor in the three tests, there is still the most common problem which transplant patients experience: the rejection of transplants. Transplant recipients must take immunosuppressants for the rest of their lives as the body will always view the new organ as a foreign object. Immunosuppressants do exactly what they say on the tin: suppress our immune system to avoid rejection of the organ, but in doing so the patient is open to infection (i.e. viruses, bacteria etc.) forever and is always at risk. Is there a way to avoid rejection and thus having to take immunosuppressants?
Some of the most interesting and promising research lies with stem cells. Stem cells are mini miracles. When we were created we were just a ball of cells, embryonic stem cells. These cells had the capability to become any cell type they wanted: heart cells, skin cells, brain cells, you name a cell and they could have been it. From this bunch of cells we formed and each cell differentiated to have a specific role. Once this role had been established, there was no turning back and that’s why you don’t have kidney cells on your skin or in your eyes. Most of the stem cells we were made from have differentiated forever, but there are still some undifferentiated ones to be found in our bone marrow (i.e. the bit in the centre of our bones). If we could grow organs from our own stem cells this would eradicate the need for immunosuppressant drugs and donors.
That’s exactly what scientists are investigating in numerous research facilities, and in 2016 this took a step towards reality at The Centre for Regenerative Medicine, Massachusetts. The research team successfully grew a beating heart from stem cells. The team had wanted to use biologically compatible material to 3D print a scaffold heart structure on which they could grow the heart tissue. Instead they went one better, taking 73 unusable human hearts and stripped them of their cells and main tissue, leaving a skeleton structure. This structure had all the necessary details making it the perfect blueprint for stem cells. The team obtained skin cells which they programmed to become stem cells once more. These were then induced to differentiate into two types of heart cell. When planted onto the scaffold and provided with nutrients, the hearts took form within two weeks and when shocked with an electric current they began to beat! The heart was still considered an immature form and could not have been transplanted just yet, but it’s the closest we’ve come to date.
If the reprogrammed skin cells were obtained from the patient in need of the transplant, this would alleviate the need for immunosuppressants as the body wouldn’t recognise the new heart as a foreign body. The reproducibility of this technique with other organs is currently underway, but it is a very promising avenue of research and holds the potential to drastically reduce the number of people who die unnecessarily due to long transplant waiting lists or lack of available matching donors. Below is a great video with Susan Lim who talks about her work in transplant surgery and also some research in the field.