Stem cells and how they can save lives
Stem cells are cells in your body that can make copies of themselves and grow into different types of cells. They’re crucial in helping replace old or damaged cells, and they also support the functions of your organs.
We all start out life as one very powerful stem cell – a fertilised egg – from which all cells of the body can be grown. Every cell ‘stems’ from a stem cell!
There are many different types of stem cells, with different capabilities, found in different areas of the body. The stem cells used in a stem cell transplant are known as blood stem cells – or technically, haematopoietic stem cells. ‘Haematopoietic’ means ‘blood forming,’ and that’s exactly what these stem cells do. They can mostly be found in the bone marrow, and they’re responsible for growing all the different types of cells needed in the blood: red blood cells, white blood cells, and platelets.
When they’re working well, your blood stem cells create millions of new blood cells every single second, making sure there is a healthy balance of the many different types of cells required for your blood and immune system to function normally. When this system goes wrong, it can lead to serious conditions like blood cancer.
Why do some people need a stem cell transplant?
When things go wrong in blood stem cells, it can cause them to produce too many blood cells that are not fully developed or can’t do their job properly. This can cause the blood and immune system to stop working and develop serious blood disorders, including blood cancers.
These conditions are often treated with chemotherapy, but sometimes a stem cell transplant is the best option to help restore a patient’s blood and immune system and eliminate any remaining cancer.
Stem cell transplants can also be used to treat genetic or autoimmune conditions that fall outside the category of blood disorders.
How does a stem cell transplant work?
A stem cell transplant involves wiping out a patient’s damaged or faulty cells using chemotherapy or radiation, before rebuilding the blood and immune system thanks to a healthy donor (or a patient’s own cells – see info box below). Donated blood stem cells are capable of establishing themselves in the patient’s bone marrow, building back up an entire blood and immune system, and even fighting any remaining cancer in the patient’s body.
Stem cells can be donated directly from the bloodstream (called Peripheral Blood Stem Cells or PBSC) or collected from the bone marrow under general anaesthetic. The donor’s blood stem cells quickly replace all the donated ones, getting back to normal levels after a few weeks.
For the patient, receiving the transplant is not the end of the journey. The donated stem cells need to establish themselves (called ‘engraftment’), during which time the patient is vulnerable to infections. Then the patient’s new immune system has to get into gear and start attacking any remaining cancer in the body. For the next few months, doctors will carefully monitor how the new immune system is doing, making sure it is active without being too active. A common side effect is called graft versus host disease (GvHD), where the body’s new immune system becomes overly active and starts attacking the patient’s healthy cells as well as cancerous ones.
Despite the quite mind-boggling fact that we can successfully replace someone’s entire blood and immune system, stem cell transplants are still a major procedure. One of our key organisational aims is to find ways to improve survival after a transplant, and our research is fundamental to a future where every patient can survive and thrive.
Did you know...
We also support patients who receive a transplant from their own cells – called an autologous transplant. This type of transplant can be the best option for patients based on their particular disease, or for patients who respond better to certain types of chemotherapy. A patient’s own stem cells are collected before they receive chemotherapy to target their diseased cells. Their stem cells are then transplanted back to the patient to help rebuild their blood and immune system.
How we match donors with patients
For a transplant to take place, we need to find a donor whose tissue type closely matches the patient’s. Someone’s tissue type is based on genes called the HLA genes. These genes are crucial in how the immune system works. They hold the code for proteins which help the immune system tell apart friendly cells from infected or cancerous cells. The HLA proteins are essential in how immune cells, especially T cells, can recognise and respond to threats.
This is why the HLA genes are so important in transplants. If they are mismatched between patient and donor, the donor’s immune cells are more likely to detect the patient’s cells as unfamiliar, and attack them as if they were a threat.
Side note: Interestingly, ‘HLA’ doesn’t technically stand for anything. There are various initialisms that people sometimes ascribe to HLA, including ‘human leukocyte antigen’ – but it is actually a combination of two different naming codes (‘Hu-1’ and ‘LA’) assigned to this family of genes.
What does a good match look like?
The HLA genes are the most varied genes we know of. Although we match for only six HLA genes for a transplant, there are tens of thousands of different variants of these six genes that have been discovered so far in humans. This level of variation helps us as a species evade a large number of different infections and cancers – but it also means that tissue types can vary wildly from person to person. Many people on the stem cell register have completely unique tissue types – meaning no one else on the register has that exact same tissue type.
An ideal match is usually a donor who has a tissue type very similar to the patient. Because you have two copies of each HLA gene (one from each parent), you possess twelve gene variants that need to be matched. This is why you might see people talking about 12/12 matches – this is a match where the donor and patient have the same twelve variants of these HLA genes.
Anything less than a 12/12 match is called a ‘mismatch,’ but that doesn’t necessarily mean it’s not good enough for a transplant. These days transplants can be successful with a lower degree of matching than ever before, thanks to advances in research and treatments.
A donor can be found from a sibling or parent, although there is only a 1 in 4 chance of an individual sibling being a full match, and parents can in almost all cases only be a half (‘haplo’) match. Alternatively, an unrelated donor from a stem cell register has potential to be a full match.
What happens if there is no match for a patient?
If a suitable related donor is not available, Anthony Nolan searches its register, and others around the world, for an unrelated donor. There are over 40 million donors on the registers worldwide and over 900,000 on the Anthony Nolan register alone.
We will also search public cord blood banks, as donated umbilical cord blood is a rich source of stem cells that can be used for a transplant.
Most patients do find a donor, but we are determined to keep working towards a future where every patient not only finds a matching donor, but the best possible donor for their treatment. Our research is key in developing new strategies in recruitment, matching and cell therapy that could make this a reality.
Why can it be harder for patients from minority ethnic backgrounds to find a matching donor?
Patients from minority ethnic backgrounds are more likely to have a relatively unique tissue type, and less likely to find a well-matched donor on UK registers, compared to those from white, northern European backgrounds.
This is because HLA genes have evolved over time based on factors like what kind of infections a population has encountered, and how populations have migrated across the world. The links between self-described ethnicity and geographical ancestry can explain why some ethnic groups have more variation in their HLA genes, and can be more likely to have a relatively rare or unique tissue type on certain registers.
We are addressing this inequity through our work in the UK and internationally to boost recruitment of donors with less well-represented tissue types, and investigate new global recruitment strategies. We also have a number of additional projects that seek to address wider inequities in stem cell transplants.
Why is the donor’s age important?
Our research shows that the age of a stem cell donor can strongly influence the outcome of a transplant – with younger donors associated with better survival rates. The biology behind this is still being investigated, but it’s possible that stem cells from younger donors cause less inflammation and fewer harmful side effects.
Based on a study of over 1,200 transplants, Anthony Nolan became the first stem cell register in the world to lower the age limit for joining to 16 and introduce an upper age limit of 31 – although once on the register, you can donate up until you’re 60.
Did you know...
Our research shows that even if everyone in the UK joined the stem cell register, there would still be people who didn’t have access to a fully matched donor. This shows just how varied tissue types can be, and illustrates why our work must go beyond recruitment alone in order help everyone access the treatment they need.
How our research helps us adapt and evolve
Over the years, our research has contributed to significant improvements in stem cell transplants – and we continue to make an impact with our long-running research.
Here are just some of the innovations in global stem cell transplant science that Anthony Nolan researchers have influenced:
- Multiple improvements in the technologies behind early tissue typing and modern genetic sequencing to help identify matching donors for patients
- The inclusion of additional HLA genes in tissue type matching to find more accurate matches
- Lowering the recruitment age as younger donors linked to better outcomes
- Matching for cytomegalovirus (CMV) status to improve outcomes
- Improvements in the global genetic database (IPD-IMGT/HLA) that underpins transplant science and matching worldwide
- A better understanding of the population genetics behind variations in the HLA genes seen across the world
And the work continues! Our research teams not only continue making advances in long-running projects, but also explore opportunities in exciting new areas of science that have the potential to transform outcomes for patients and donors.
Did you know...
The IPD-IMGT/HLA Database contains over 40,000 different variants of the HLA genes, and is growing all the time. It is accessed over a million times a year by scientists and transplant providers to make sure they are using the most up-to-date versions of HLA genetic sequences.
The next generation of treatments: Cell and gene therapies
Cell and gene therapies have the potential to be the future of medicine for many diseases.
A stem cell transplant is itself classified as a cell therapy, because it uses live stem cells – but many more types of cell therapies are being developed or are already being used in patients. Cell therapies have an advantage over typical medicines, in that cells are considered ‘living drugs’ that can continue having multifaceted benefits for as long as they remain in a patient.
When a cell therapy also involves genetic manipulation – typically genetic engineering of cells in a laboratory before they’re infused into a patient – it can also be called a gene therapy. Casgevy, a groundbreaking therapy for sickle cell disorder and beta-thalassaemia, falls under this category.
One increasingly used cell therapy for blood cancers in the UK is CAR-T therapy. This involves T cells (an important type of immune cell) being collected from a patient, before being genetically modified in a lab to more effectively fight cancer. The cells are then returned to the patient, where they ideally will eliminate any remaining cancer. There are currently several forms of CAR-T offered through the NHS, and many more are being developed.
Cell and gene therapies like Casgevy and CAR-T offer the hope of a potential cure for some patients who do not have any other options available.
How is Anthony Nolan helping to develop these new therapies?
Our Policy and Public Affairs team continue to campaign for the uptake of cell and gene therapies on the NHS, to provide more options for patients. Our close work with patients and healthcare providers helps us make strong cases to policy makers.
Our Immunotherapy group is actively researching new cell therapies that could help treat transplant complications or be used alongside stem cell transplants. Their work is helping to build our foundational understanding of what
We also support the development of new cell and gene therapies through our Cell Therapy & Laboratory Services (CT&LS), which provides cells from Anthony Nolan donors to cell therapy developers in the pharmaceutical and biotech space. Anthony Nolan donors can sign up to be donors for medical research & treatments, allowing their cells to make a difference for potentially hundreds or thousands of future patients.
Did you know...
Casgevy uses the Nobel prize-winning CRISPR technology to make gene edits to blood stem cells. CRISPR was discovered in bacteria as a defence mechanism in viruses, and has been adapted to allow scientists to make very precise modifications to DNA.