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iPS cells and reprogramming: turn any cells of the body into a stem cell

Reprogramming allows us to turn any cell of the body into a pluripotent stem cell, and then into any other type of cell. The discovery of reprogramming in 2006 changed the scientific community’s thinking about how cells work. Reprogramming has opened up exciting possibilities for studying and treating disease. 

Discovery of iPS cells

In 2006, Shinya Yamanaka made a ground-breaking discovery. He found a new way to ‘reprogramme’ adult, specialised cells and turn them back into stem cells. These laboratory-grown stem cells are pluripotent – they can make any type of cell in the body - and are called induced pluripotent stem cells, or iPS cells. Only embryonic stem cells (ESCs) are naturally pluripotent. Yamanaka’s discovery means that, theoretically, any dividing cell of the body can now be turned into a pluripotent stem cell. He was awarded the Nobel Prize in Physiology or Medicine just six years after this discovery. 

 

So how are iPS cells made? Yamanaka collected mouse skin cells, added four genes, and grew these altered cells in the laboratory. This started a process inside the cells called reprogramming or dedifferentiation. Within 2 – 3 weeks, the skin cells were converted into induced pluripotent stem cells. Scientists can now also do this with human cells, by adding even fewer than four genes.

iPS cells and disease

Portrait of Shinya Yamanaka

Shinya Yamanaka first discovered iPS cells in 2006 and won a Nobel Prize for the work in 2012

An important step in developing a therapy for a given disease is understanding exactly how the disease works. What exactly goes wrong in the body, and where? To do this, researchers need to study the cells or tissues affected by the disease. This is not always as simple as it sounds. 

For example, it’s almost impossible to collect brain cells from patients with Parkinson’s disease, especially in the early stages of the disease before the patient is aware of any symptoms. Reprogramming means that scientists can now get access to large numbers of the type of neurons (brain cells) that are affected by Parkinson’s disease. Researchers first make iPS cells from, for example, skin biopsies (of specialised cells) from Parkinson’s patients. They then use these iPS cells to grow neurons in the laboratory. The neurons have the same genetic make-up as the patients’ own cells. This way, scientists can directly work with neurons affected by Parkinson’s disease in a dish. They can use these cells to learn more about what goes wrong inside the cells and why. Cellular ‘disease models’ like these can also be used to search for and test new drugs to treat or protect patients against the disease. 

Diagram showing the creation and applications of iPS cells

iPS cells - derivation and applications: Certain genes can be introduced into adult cells to reprogramme them. The resulting induced pluripotent stem cells resemble embryonic stem cells and can be differentiated into any type of cell to study disease, test drugs or-after gene correction-develop future cell therapies

Future applications and challenges

Reprogramming holds great potential for new medical applications, such as cell replacement therapies. Since iPS cells can be made from a patient’s own skin, they could be used to grow specialised cells that exactly match the patient. This means they would not be rejected by the immune system.If a patient has a genetic disease, the genetic error could be corrected in their iPS cells in the laboratory. These ‘corrected’ iPS cells could be used to grow a patient-specific batch of healthy specialised cells for transplantation. But this benefit remains theoretical for now. 

Until recently, making iPS cells involved permanent genetic changes inside the cell. These changes can cause tumours to form. Scientists have now developed methods for making iPS cells without this genetic modification. These new techniques are an important step towards making iPS-derived specialised cells that would be safe for use in patients. 

Further research is now needed to understand fully how reprogramming works and how iPS cells can be controlled. This will allow researchers to develop cells which are consistent in their behaviour.  This is essential to meet the high quality and safety requirements for use in the clinic. 

 

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