The discovery of iPS cells

In 2006, Shinya Yamanaka made a groundbreaking discovery that would win him the Nobel Prize in Physiology or Medicine just six years later: he found a new way to reprogramme adult, specialized cells to turn them 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 are naturally pluripotent. Yamanakas discovery means that theoretically any dividing cell of the body can now be turned into a pluripotent stem cell.

So how are these iPS cells made? Yamanaka added four genes to skin cells from a mouse. This started a process inside the cells called reprogramming and, 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.

This short clip introduces the science behind reprogramming. View the full 16-minute film to see the whole story of Shinya Yamanaka's discovery.

IPS cells and embryonic stem cells are very similar. They are self-renewing, meaning they can divide and produce copies of themselves indefinitely. Both types of stem cell can be used to derive nearly any kind of specialized cell under precisely controlled conditions in the laboratory. Both iPS cells and embryonic stem cells can help us understand how specialized cells develop from pluripotent cells. In the future, they might also provide an unlimited supply of replacement cells and tissues for many patients with currently untreatable diseases.

In contrast to embryonic stem cells, making iPS cells doesnt depend on the use of cells from an early embryo. Are there any other differences? Current research indicates that some genes in iPS cells behave in a different way to those in embryonic stem cells. This is caused by incomplete reprogramming of the cells and/or genetic changes acquired by the iPS cells as they grow and multiply. Scientists are studying this in more detail to find out how such differences may affect the use of iPS cells in basic research and clinical applications. More research is also needed to understand just how reprogramming works inside the cell. So at the moment, most scientists believe we cant replace ES cells with iPS cells in basic research.

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? To do this, researchers need to study the cells or tissues affected by the disease, but this is not always as simple as it sounds. For example, its almost impossible to obtain genuine brain cells from patients with Parkinsons disease, especially in the early stages of the disease before the patient is aware of any symptoms. Reprogramming means scientists can now get access to large numbers of the particular type of neurons (brain cells) that are affected by Parkinsons disease. Researchers first make iPS cells from, for example, skin biopsies from Parkinsons patients. They then use these iPS cells to produce neurons in the laboratory. The neurons have the same genetic background (the same basic genetic make-up) as the patients own cells. Thus scientist can directly work with neurons affected by Parkinsons 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.

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

Until recently, making iPS cells involved permanent genetic changes inside the cell, which 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 specialized 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 and produced consistently enough to meet the high quality and safety requirements for use in the clinic.

February 2013 Nature news article on planned clinical trial using iPS cells Stem cells the future: an introduction to iPS cells Research into reprogrammed stem cells: an interactive timeline Stem cell school - multimedia learning module on cellular reprogramming Alzheimer Research Forum 4-part article on iPS cells and disease (September 2010) Nature news feature on challenges in the iPS field (May 2011)

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