• STEM CELLS AND THE PANCREAS

     

    SC Research: CBS

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    What do we know?

    When blood glucose (sugar) levels rise, beta cells in the pancreas release insulin. Insulin tells cells throughout the body to take up glucose from the blood.

    In Type 1 diabetes, the immune system destroys beta cells. In Type 2 diabetes, cells do not take up enough glucose, either because they are insensitive to insulin or too little insulin is produced.

    Type 1 diabetes patients require daily blood testing and insulin shots.

    Scientists have successfully used pluripotent stem cells to produce glucose-responding cells that release insulin, like beta cells. Clinical trials of these cells are underway.

    What are researchers investigating?

    Diabetes is quite well understood, but the causes of diabetes are not. Research is still being conducted on what triggers the immune system to destroy beta cells in Type 1 diabetes.

    Current research is examining the use of stem cells as a way to create beta cells that can be transplanted into patients with Type 1 diabetes. Clinical trials are presently taking place with devices/capsules that protect the new beta cells from the patient’s immune system.

    Researchers are also interested in the possibility of using drugs to promote cells in a patient’s pancreas to naturally make more beta cells.

    What are the challenges?

    Autoimmunity is a big challenge for Type 1 diabetes. Even if new beta cells are created or transplanted into a patient, the immune system will eventually target and destroy these cells. Thus, treatments must consider how to prevent new beta cells from being targeted. Typically this has involved immune suppressants, which have an unfortunate side effect of increasing the risk of infection.

    How is Diabetes treated Now?

    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 administer insulin when it is needed (through injections or a pump). Unfortunately it can still be hard to keep the blood sugar level normal. 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 is too low (hypoglycaemia) which can be fatal.

    It is possible to treat Type 1 diabetes by transplanting isolated islet cells, containing beta 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 administrating insulin is no longer needed. Islet transplantation is more common as a whole pancreas transplant involves major surgery and carries significant risk.

    Isolated islets of Langerhans used for transplantation
    Isolated islets of Langerhans used for transplantation 

    There are problems with islet transplantation:

    • The number of donors is heavily outweighed by the demand and the islets have to be of good enough quality and in the right amounts.
    • Transplants require the immune system to be suppressed so that the new ‘foreign’ organ is not rejected. The immune suppressing drugs leave the recipient vulnerable to infection and often have side-effects. Today only a limited number of type 1 diabetic patients are suited for transplantation due to these side effects.

    Even with immune suppressing drugs the transplant is eventually destroyed by the immune system and further transplants are needed. As the immune system has developed to destroy these types of cells from the first transplant, it recognises foreign cells more quickly and easily. This means further islet transplants and other organ transplants like the kidney are more likely rejected.

    Human Islet of Langerhans
    Human Islet of Langerhans: The same Islet, shown on the left with insulin highlighted in green revealing the beta cells. On the right glucagon is highlighted in purple, produced from alpha cells.

    Are stem cells used in the treatment of Diabetes?

    There are currently no proven treatments for diabetes using stem cells. If beta cells could be made in the lab it could solve the problem of obtaining the right number and quality of islets for transplant.

    Current Research

    Current approaches to make new beta cells for therapy:

    • Mature pluripotent stem cells into beta cells in the lab, which are transplanted into diabetic patients.
    • Mature beta cells in the lab from other types of cells, for example liver cells, which are transplanted into diabetic patients.
    • Use drugs to trigger cells in the diabetic patient’s own pancreas to produce new beta cells.

    And, for all of these approaches ongoing research is exploring:

    • How can we protect the cells from being attacked by the immune system once they have been transplanted?
    Insulin-producing cells made from human embryonic stem cells
    The unseen world: Insulin-producing cells made from human embryonic stem cells

    Making beta cells from pluripotent stem cells

    Pluripotent cells (either embryonic stem cells or induced pluripotent stem cells) can make any cell type in the body and researchers are exploring how to direct these to make fully functional beta cells. Such cells could replace the scarce source of donor pancreatic islets of Langerhans. Researchers have recently succeeded in producing cells from human pluripotent stem cells that respond to glucose in a similar way to normal beta cells both in the laboratory and in diabetic mice after being transplanted. These beta cells will soon be tested for safety in phase 1 clinical trials.

    Making beta cells from other cells

    Some researchers think it might be possible to encourage cells already present in the patient’s pancreas to make new beta cells. It is not known whether stem cells exist in the pancreas but beta cell progenitors have been found. Researchers hope they may be able to find drugs that can activate the progenitor cells in the body of a diabetes patient, or reprogramme other mature pancreas cells to produce more beta cells. Reprogramming other cells, for example, skin cells or liver cells, to make beta cells in the lab is also a possibility. These efforts are still experimental in nature and have not reached a point where clinical trials are close.

    Beta cell pathways diagram
    The birth of beta cells: The pathway of maturation from progenitor cells to beta cells as the pancreas develops.

    Protecting cells from the immune system

    Capsule for transplanting cells
    Capsule for transplanting cells that protects them from the person’s immune system: created by ViaCyte and currently being tested in a phase 1/2 clinical trial

    Work is underway to find the most effective way of encapsulating transplanted cells to protect them from immune attack. At the moment several research groups and commercial companies (ViaCyte and Beta-O2Technologies) are involved in clinical phase 1 studies to create a capsule that allows for outward movement of insulin yet protects the cells from the immune system.

    Work exploring drugs that reduce the immune reaction is also underway. Results of this work could create better therapies for any beta cell source.

    Current Clinical Trials

    Transplanting progenitor cells made from pluripotent cells

    The first clinical trial for diabetes Type 1 involving stem cells started in July 2014 and is run by ViaCyte. The trial is a Phase 1/2 clinical trial testing for safety and efficacy. Progenitor cells are being placed in a credit card-like case and transplanted into the body. The hope is that similar to in mice the progenitor cells will spontaneously mature into insulin producing cells in the body, with the case allowing for the dispersal of insulin whilst preventing the immune system from attacking the cells. If successful, this could prevent the need for immunosuppressant drugs reducing the risk of further infection after surgery.

    RESOURCES

    Diabetes Atlas – statistics from the International Diabetes Federation (IDF)

    International Diabetes Federation

    Innovative Medicines Initiative for Diabetes (IMIDIA)

    Diabetes UK – information and patient support

    My Life – information for younger people living with diabetes

    HumEn – research partnership that aims to develop insulin-producing beta cells from stem cells, for diabetes

    Centre for beta cell therapy – research consortium

    ViaCyte – information about the first human clinical trial for diabetes

    Islet isolation and transplantation – information and videos from the Nordic Network of Islet Transplantation

    Classroom resource about stem cells and diabetes using real science data

     

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