Blood stem cells: the pioneers of stem cell research

Leukaemias and lymphomas are malignant cancers caused by uncontrolled growth of blood-forming cells. Some types of leukaemias and lymphomas are relatively easy to treat. However, others still give very poor prognosis.  

Scientists are studying how leukaemias and lymphomas develop, to identify targets for new therapies. This research often focuses on pre-cancer syndromes, such as myelodysplastic syndrome. In these cases, patients are diagnosed early, and their condition is monitored.  In many cases their disease will progress to leukaemia, and then the chances of the successful treatment are very low. 

If scientists are able to better understand the mechanisms in HSC which lead to  leukaemia development and progression, they can create better treatment strategies. 

One of the major problems in the use of HSC in therapy is the side effects of HSC transplantations. Many research projects and clinical studies are dedicated to finding better ways of isolating HSC and preparing the patient for transplantation. 

For a HSC transplantation to be successful, the patient’s own HSC must be destroyed, to make space for the transplanted HSC. To achieve this, patients are treated with chemotherapy and/or full-body radiation. Those treatments affect not only HSC, but also many other cells and tissues in the body. The patient’s immune system is severely weakened, and they are susceptible to infections. This is why scientists are trying to develop methods of removing HSC from their niche without using chemo- or radiotherapy. One such new methods is using drugs (antibodies), which weaken the interactions between HSC and their niche in the bone marrow, causing them to leave. This approach is currently being tested in clinical trials. 

One of the most serious complications of stem cell transplantation is graft-versus-host disease (GVHD). This is a condition where transplanted immune cells attack the patient’s own tissues. This happens because the donor-derived immune cells recognise patient’s antigens as foreign, or ‘non-self’, and react as though the patient’s cells are an infection to fight. To make HSC transplantations safer, doctors need to be able to minimize the risk of GVHD.  

When considering using HSC transplant to treat cancers, scientists are trying to establish a proper balance between avoiding GVHD and achieving anti-tumour effect of the transplanted cells. In other words, they are trying to find a way to stop the transplanted cells from attacking healthy tissues, but at the same time not to prevent the transplanted cells from fighting the cancer cells.  

Red blood cells carry oxygen around the body. Patients who lose a lot of blood need to have it replaced straight away by a blood transfusion. There are not enough blood donors to meet patient needs, so researchers are looking for an alternative solution. 

Since pluripotent stem cells have the potential to make any cell type of the body, they could potentially provide an unlimited supply of red blood cells. It is already possible to make small numbers of red blood cells from pluripotent stem cells in the lab, and the first clinical trial of lab grown erythrocytes transfusions began in Autumn 2022. The next challenge is to develop techniques for producing the large numbers of red blood cells that are needed for transfusion.  

HSC transplantations are standard treatment for certain blood disorders, such as leukaemia or lymphoma. Clinical trials of HSC transplantations for other diseases are ongoing. There are potentially many diseases which could be treated by HSC transplantation, including AIDS and autoimmune diseases, such as diabetes. However, the risk of side effects associated with transplantation are still high enough to prevent use of HSC transplantations for patients who have other treatment options.  

To use HSC transplantations more widely, scientists need to establish safer methods of preparing the patient for the stem cell transplantation and better methods of isolation of pure HSC, without donor’s immune cells. In the future, it may be possible to generate HSC from patient’s own cells (for example using iPS cells).

Finding a proper donor of HSC is sometimes challenging, so scientists are searching for ways to grow a limitless supply of blood stem cells. One possibility might be to collect stem cells from the bone marrow, then grow and multiply them in the lab. Researchers are also trying to make blood stem cells from embryonic stem cells or induced pluripotent stem (iPS) cells. iPS cells could be made from a patient’s own skin and then used to produce blood stem cells. This would overcome the problem of immune rejection.