Diabetes is a common life-long condition and the number of children being diagnosed with type 1 diabetes is increasing. The symptoms can be controlled but there is no cure. For many, diabetes means living with daily insulin injections and the possibility of long-term damage to their health. How might stem cells help?
Around 78,000 children develop type 1 diabetes worldwide each year; 24% of these are in Europe.
Insulin-containing beta cells (white); beta cells derived from cells that may act as progenitors (green); duct cells (red)
Leonard Thompson, the first human to be successfully treated for diabetes using insulin, aged 14 in January 1922
All the cells in your body need energy to survive. This energy is carried around the body as sugar (glucose) in the blood. Normally, blood sugar levels are controlled by the release of the hormone insulin. Insulin is made by cells in the pancreas called beta cells that are arranged into structures called Islets of Langerhans. In one human pancreas there are roughly one million Islets of Langerhans. The insulin produced by these cells transfers sugar from the blood stream into cells around the body so that it can be used for energy.
In diabetes, the body does not make enough insulin and/or doesn’t respond to it properly. Type 1 diabetes occurs when the body’s immune system attacks the pancreatic beta cells so that they become damaged and can no longer make insulin. This means the levels of sugar in the blood stay high all the time, which can lead to long-term damage to the body.
Currently there is no cure for diabetes. Although type 2 diabetes can often be at least partially controlled by a healthy diet and regular exercise, type 1 diabetes cannot. People with type 1 diabetes must test their blood sugar levels several times a day and inject insulin when it is needed. Unfortunately it can still be hard to keep the sugar level normal, even with regular injections. Over time, high blood sugar levels can cause serious damage to the heart, eyes, blood vessels, kidneys and nerves, whilst injecting too much insulin can lead to a blood sugar level that’s too low (hypoglycaemia) and this can be fatal.
It is possible to treat type 1 diabetes by transplanting islet cells or even a whole pancreas into the patient from a donor. Transplants can enable the body to regain control of blood sugar levels so that insulin injections are no longer needed. Islet transplantation is becoming more common because whole pancreas transplants involve major surgery and carry significant risk. However, the number of donors is heavily outweighed by the demand and transplants require the immune system to be suppressed so that the new ‘foreign’ organ is not rejected. Immune suppressing drugs leave the recipient vulnerable to infection and often have side-effects.
One of the biggest problems faced by islet transplantation is the lack of donors. Instead of using donor cells, new beta cells could be grown from stem cells and used in replacement therapy. There are several different ideas about where to get these stem cells and how they could be used:
Embryonic stem cells
Human embryonic stem (ES) cells could be differentiated into immature beta cells for transplantion into a diabetes patient, where it is hoped the cells would mature and produce insulin. Researchers have shown that this is possible in mice. The transplanted immature cells, sometimes called beta cell precursors, differentiate further once in the mouse and are then able to sense sugar levels in the blood and respond by releasing insulin. However, precursor cells have the potential to form tumours so their safety must be established before this approach can be used in humans. An alternative would be to make fully differentiated and functioning beta cells for transplantation, but much more research is needed to understand how to make and purify these cells.
Reprogrammed cells (or iPS cells)
It may be possible to treat diabetes using induced pluripotent stem (iPS) cells made by reprogramming the patient’s own adult cells. These iPS cells could be used to make beta cells to give back to the patient. Scientists have shown that it is possible to create insulin-producing cells from primate iPS cells, and some of these lab-grown insulin-producing cells are able to regulate blood sugar levels in diabetic mice. So far these iPS-derived cells have been less successful at producing insulin than beta cells made from embryonic stem cells. However, using iPS cells could solve the problem of transplant rejection – the transplanted cells would be made from a sample taken from the patient’s own body so should not be attacked as ‘foreign’. Even so, the body might still attack the cells because of the original disease problem – type 1 diabetes causes the immune system to attack even the body’s own pancreatic beta cells.
Stem cells in the patient's own body
Some researchers think it might be possible to encourage the stem cells already present in the patient’s pancreas to make new beta cells. The first challenge for this approach is to find the stem cells in the pancreas. Beta cell progenitors have been found in the pancreas of both rodents and humans; progenitor cells have some stem cell properties but cannot self-renew (copy themselves) indefinitely. Beta cell progenitors can be made to produce new mature beta cells in the lab, but more research is needed to understand how this works. Researchers hope they may be able to find drugs that can activate the progenitor cells in the body of a diabetes patient.
As well as developing methods for making new beta cells, scientists are investigating ways to make sure the cells survive after transplantation. Since type 1 diabetes involves the destruction of beta cells by the body’s immune system, current research is looking at how to protect transplanted cells from this kind of damage. This could be done by inserting the cells into the patient inside a protective capsule, or transplanting them into a part of the body where the immune system is less aggressive. It may also be possible to use stem cells from the patient’s own bone marrow to ‘re-educate’ the immune system so that it no longer attacks the beta cells. This has already been tested in a small number of patients in a phase I clinical trial, with some positive results. Further research is needed to establish whether the technique can be developed into a safe and effective therapy.
It is hoped that clinical trials using beta cells grown from human embryonic stem cells will begin in the next few years. Currently scientists are working to make sure the transplanted cells will be safe and efficient at controlling blood sugar levels. The new beta cells must be able to sense blood sugar levels and react accordingly. The main problem to be overcome now is how to stop the immune system destroying the transplanted cells without using immune suppressing drugs.
March 2013 news article on research into treating diabetic wounds with mesenchymal stem cells
Diabetes in Europe 2012 statistics from the International Diabetes Federation
International Diabetes Federation
Diabetes UK - information and patient support
My Life - information for younger people living with diabetes
What is diabetes? Video explaining the disease
Centre for beta cell therapy - research consortium
Clinical trials database listing for a diabetes trial using stem cells from the bone marrow
Classroom activity about cell therapy for diabetes