The discovery of iPS cells

In 2006, Shinya Yamanaka made a remarkable discovery: he found a way to make a new kind of stem cell in the laboratory. This cell is pluripotent – it can make any cell type of the body - and is called an induced pluripotent stem cell, or iPS cell. Only embryonic stem (ES) cells, derived in humans from a 4-5 day embryo, are naturally pluripotent. Yamanaka’s discovery means that any cell of the body except a sperm or egg 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. We can now do this with human cells, even by adding only three genes.

iPS cells and embryonic stem cells

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

In contrast to embryonic stem cells, making iPS cells doesn’t depend on the destruction of an early embryo. Are there any other differences? Research indicates that some genes in iPS cells may behave in a slightly different way to those in embryonic stem cells. Scientists are studying this in more detail to find out exactly what the differences between the two cell types are, and whether they are important. So at the moment, we can’t replace ES cells with iPS cells in basic research.     

iPS cells - derivation and applications: iPS cells can be made from adult cells by introducing specific genes. Cells are reprogrammed and become pluripotent, resembling embryonic stem cells. iPS cells can be differentiated to any cell type and used for transplantation in cell replacement therapy. Disease-affected cells made from iPS cells can be used as disease models in research and to test new drugs.

iPS cells and disease

With reprogramming, scientists can specifically create stem (iPS) cells from people with diseases like Parkinson’s and Huntington’s, then use these iPS cells to make disease-affected specialized cells. In many cases, there’s no other way to get the specialized cells.  It’s not possible to study the actual brain cells of a Parkinson’s patient, for example, but scientists can now make iPS cells from people with Parkinson’s disease and use them to produce diseased neurons in the laboratory. The lab-made cells can help us learn more about the disease and its effects. Cellular disease models like these can also be used as a test system for the development of new drugs.

Future applications of iPS cells

iPS cells hold great potential for regenerative medicine.  By using specialized cells made from a patient's own iPS cells to replace lost or damaged cells in the body, it is possible to avoid immune rejection. In such cell replacement therapy, the cells given to the patient would be recognized as the body's own. But this benefit remains theoretical for now. Making iPS cells currently involves genetic modification, which can introduce DNA mutations that cause tumor formation. Scientists are working to develop methods for making iPS cells without genetic modification so that iPS-derived cells may safely be used in the clinic.  One possibility is to apply proteins or chemicals instead of genes, to initiate the process of reprogramming without having a permanent effect on the cell’s DNA.

Find out more

Stem cell school - multimedia learning module on cellular reprogramming
Research into reprogrammed stem cells: an interactive timeline
Shinya Yamanaka's discovery of iPS cells - original scientific paper
Alzheimer Research Forum 4-part article on iPS cells and disease (September 2010)
Nature news feature on challenges in the iPS field (May 2011)

Acknowledgements and references

This factsheet was created by Manal Hadenfeld and reviewed by Oliver Bruestle.
Shinya Yamanaka photograph by Rubenstein.  Additional images by Michael Peitz, Johannes Jungverdorben and Michael Rossbach.