GENE THERAPY BASICS
The human body contains over 200 different specialised cell types, such as muscle, bone or brain cells. These cells carry out specific functions within the body, necessary for the health of an organism. Injury, disease or ageing can lead to the loss of specialised cells from the body. In many cases, such loss is irreversible, meaning that the diseased or lost cells can no longer be replenished by healthy ones.
Cell therapy aims to introduce new, healthy cells into a patient’s body, to replace the diseased or missing ones. A challenge for this type of therapy is having enough cells for transplantation into a patient and reaching the targeted tissue (muscles for example). This is because specialised cells, such as brain cells, are difficult to obtain from the human body. Also, specialised cells typically have a limited ability to multiply, making it difficult to produce sufficient numbers of cells required for certain cell therapies. Some of these issues can be overcome through the use of stem cells.
How are stem cells used to develop cell therapies?
Stem cells are unspecialised cells that have the ability to develop into other functional cell types. Importantly, some types of stem cells can be grown outside of the human body, thus allowing the production of a large number of cells required for successful applications of cell therapy in medicine. Two main types of stem cells are being explored in the context of cell therapy: pluripotent stem cells and tissue-specific (also referred to as adult) stem cells.
Pluripotent stem cells can produce any cell type in the human body. Therefore, pluripotent stem cells provide a potential source of cells that are otherwise inaccessible or present in low numbers in human bodies. They can also be maintained and multiplied outside the human body for extensive periods of time. Depending on their origin, two types of pluripotent stem cells can be distinguished: embryonic stem cells and induced pluripotent stem cells. Embryonic stem cells are derived from early embryos, whereas induced pluripotent stem cells are derived by using a method called ‘reprogramming’, which turns specialised cells into cells very much like embryonic stem cells
Unlike pluripotent stem cells which have the ability to give rise to any human cell type, tissue-specific stem cells give a much more limited repertoire of functional cell types. For example, blood stem cells give rise to other types of blood cells, but do not typically produce cells found outside of the blood system.
To obtain specialised cell types, either pluripotent or tissue-specific, stem cells are grown in a laboratory and treated with cocktails of molecules, which provide signals for their development into functional cells.
Have cell therapies been successfully used?
Some cell therapies have been successfully used for many years now. The oldest example is the bone marrow transplant, which is routinely used in medicine to effectively treat certain diseases of the blood and immune system, such as leukaemia, lymphoma and myeloma. The bone marrow transplant contains blood stem cells which can replenish the blood and immune system upon transplantation into the recipient. This type of stem cell treatment has provided an important proof-of-principal for using cell therapies to treat patients.
More recently, stem cells from the eye (limbal stem cells) have also been used to treat eye injuries. In some cases, stem cells are first modified by gene therapy to correct the mutation causing the disease. Once the disease-causing mutation is corrected, the cells are delivered to patients to repopulate the diseased areas of their body. This so-called combined cell and gene therapy allowed the development of therapies for blood disorders, including some types of leukaemia, lymphoma, severe combined immunodeficiency and β-thalassemia.
What is on the horizon for cell therapy applications?
The ability to turn human stem cells into specialised cell types, such as cells of the brain, eye or pancreas, has opened up possibilities for developing treatments for many degenerative diseases. For example, several clinical trials are currently under way to treat Parkinson’s disease using pluripotent stem cell-derived brain cells. Parkinson’s disease is caused by the loss of a particular brain cell population that produces the chemical dopamine. The loss of these cells from the area of the brain called the substantia nigra leads to movement disorders, tremors and muscle rigidity. To replace the missing cells, scientists are deriving dopamine-producing brain cells from human pluripotent stem cells. The stem cell-derived brain cells are currently being tested in clinical trials to check whether they eradicate the symptoms of the disease. Similarly, scientists are testing the utility of using stem cell-derived cells of the eye to treat some blindness-causing diseases, such as age-related macular degeneration.
For cellular therapies to be a clinical success, it is important to have well-established procedures for creating the desired cell types in required quantities. It is also important to ensure that the transplanted cells can survive upon transplantation into the patient and integrate into the body to perform their functions. In addition, it is necessary to ensure that transplanted cells do not multiply too much, as this could create tumours in patients. This is why rigorous testing has to be done before cellular therapies become available to patients.
Last updated: 27 May 2021