10 breakthroughs in stem cell research
Stem cells could help cure heart failure. Christie Norris looks at major developments over the last three decades and the role the BHF is playing.
1989: The first “‘knockout”’ mouse
“Knockout” mice are bred to lack specific genes, which helps scientists find out which genes are linked to different diseases. By removing a particular gene, a disease similar to that seen in humans develops in the mouse. This helps scientists learn more about how diseases develop, what symptoms occur, and how they can be treated. The work of Mario Capecchi at the University of Utah, Oliver Smithies at the University of North Carolina and Martin Evans at Cardiff University led to the development of the first ‘knockout’ mouse in 1989 - they went on to be awarded the 2007 Nobel Prize in Physiology or Medicine.
Knockout mice are now considered vital to disease research. Thanks to this discovery, BHF Professor Hugh Watkins, Director of the British Heart Foundation Centre of Research Excellence at Oxford University, is looking at genes associated with coronary heart disease.
1998: Embryonic stem cells
Our understanding of stem cells began with embryonic stem cells. They come from a ball of cells called the blastocyst, which forms five days after an egg is fertilised and develops into the embryo. Embryonic stem cells were isolated from mice in 1981.
In 1998, Professor James Alexander Thomson and his team at the University of Wisconsin–Madison grew the first human embryonic stem cells in a laboratory dish (in vitro). This allowed scientists to learn how the cells function.
Women who undergo IVF can donate ‘spare’ embryos, which would otherwise be destroyed. Only embryos at an early stage of development (up to 14 days) can be used, and there are strict guidelines for how they can be used.
2001: Making beating heart cells
In 2001, Professor Christine Mummery and her team in the Netherlands used stem cells to create beating heart cells outside the body for the first time. Her team is now working to grow a small piece of human heart from stem cells.
Stem cells could produce red blood cells for transfusion
This will let us study causes of diseases, especially genetic causes. It will also improve development of medicines that are usually tested on animals, as animal hearts work differently.
Researchers at the BHF Centres of Regenerative Medicine are working to develop new treatments for diseased hearts. The centres are collaborations between top universities, including Edinburgh, Bristol, Oxford and Cambridge cardiac stem cells.
2002: Making new heart muscle
In 2002, researcher Chunhui Xu and team at Emory University School of Medicine in Atlanta found that human embryonic stem cells can be made to form heart muscle cells. This discovery encouraged scientists to explore whether embryonic stem cells could be used to make new heart muscle for heart attack patients. When a person has a heart attack, blood flow to the heart is restricted or blocked which can cause heart cells to die. Although less commonly used than other cell types, embryonic stem cells have helped researchers explore new ways of using stem cells to fix our hearts
2003: Discovery of cardiac stem cells
Helping the heart regenerate itself after damage is a dream of cardiovascular researchers. Scientists thought the heart didn’t have its own stem cells, until Professor Antonio Beltrami at the University of Udine in Italy described a small population of stem cells in the heart in 2003.
Building on this discovery, BHF Professor Michael Schneider, at Imperial College London, is investigating how these stem cells can be ‘instructed’ to form new heart muscle, meaning the heart might be able to repair itself.
2004: Making heart cells from fats
In 2004, Valérie Planat-Bénard and colleagues at Paul Sabatier University in Toulouse, France, found that heart-like cells could be made from fat cells which lie just beneath the skin (adipose tissue). When compared to embryonic stem cells, fat cells are considered an easier and quicker means of making heart muscle cells in the lab
2007: Making heart cells from skin
A revolutionary breakthrough in stem-cell biology was the ability to make induced pluripotent stem (iPS) cells, with properties very similar to embryonic stem cells.
In 2007, researcher Dr Shinya Yamanaka at Kyoto University found that human skin cells, which are easy to isolate, can be transformed directly into iPS cells.
Professor Sian Harding, at Imperial College London, is just one of the BHF-funded scientists using iPS cells as a resource to make new heart cells. We can use iPS cells to study inherited heart conditions.
The BHF is also funding Professor Chris Denning’s team at the University of Nottingham, which is growing cells from patients to examine how genetic mutations affect heart cell behaviour. Without stem cells, this work would only be possible using a biopsy of the patient’s heart.
2010: Waking up our hearts
Now that stem cells have been discovered in the heart, the challenge is to ‘wake them up’ so they’re ready to repair damage. BHF scientist Dr Nicola Smart, at the University of Oxford, has found new methods of ‘waking up’ the heart’s stem cells.
BHF researchers aim to cure heart failure by using stem cells to make new, healthy heart cells
She has shown that a protein called thymosin beta-4 can encourage cells to move towards damaged tissue and help form new muscle cells and blood vessels.
2013: Patches for damaged hearts
Using bacteria sounds an unlikely way to grow new heart cells, but that’s exactly what Professor Ipsita Roy is doing. Professor Roy, from the University of Westminster, has developed bacteria-derived materials (polymers) that can be used inside the human body.
These polymers have been made into ‘patches’ with special coatings that encourage the growth of different types of cells. Researchers are now collaborating with cardiac surgeons to find the most effective ways of attaching these polymer patches onto areas of damaged heart muscle. Once there, the patch will repair the damage. Professor Roy is part of the BHF-funded Centre of Regenerative Medicine that is led by Imperial College and focused on cardiac tissue engineering.
2016: New blood
Researchers, led by Dr Jo Mountford of the Scottish National Blood Transfusion Service and the University of Glasgow, are scaling up generation of red blood cells from stem cells to make a limitless supply of clean blood for transfusion. This could help those who lose blood through surgery or injury.
What are stem cells?
There are two types of stem cells: those found in embryos and those found in adults. Embryonic stem cells have the potential to develop into any part of the body. As an embryo grows, most cells become specialised. This means they change into a specific part of the body, such as heart muscle cells, red blood cells or liver cells. This change is permanent.
The remaining unspecialised cells are adult stem cells. If damage occurs in certain parts of the body, they repair it by developing into the specific type of cell required. They can also replicate to produce more cells as needed. This happens naturally in some parts of the body, such as the intestine and bone marrow, but doesn’t generally happen in the heart.
Unfortunately, a heart attack, where oxygen supply to the heart is restricted, causes heart cells to die. This can lead to heart failure, a debilitating condition where the heart can no longer pump blood around the body as efficiently as it normally would.
Through our Mending Broken Hearts Appeal, BHF researchers aim to cure heart failure by using stem cells to make new, healthy heart cells.
Heart failure: a human problem
People living with heart failure, like Anne Gayfer (pictured), can experience shortness of breath and fatigue on a daily basis.
There are over half a million people in the UK living with heart failure, which is why we’re working so hard to find a cure.
Read Anne’s story on living with heart failure and get tips to help manage heart failure symptoms or order our May/Jun 2015 issue on 0870 600 6566. You can also call to order our free Living with heart failure booklet, or download it at the BHF publications page.