Dolly the sheep was not born a traditional lamb, but rather as the first ever clone of an adult cell. As well as being a scientific breakthrough in her own right, she also inspired another landmark discovery – induced pluripotent stem (iPS) cells. The key element of iPS cell development is that the genome is reprogrammed, just as Dolly’s DNA was reprogrammed when she was cloned. Reprogramming a cell’s DNA erases the cell’s specialisation and forces it to become pluripotent, which makes the cell capable of forming all the different cell types found in an organism. Professor Shinya Yamanaka and his postdoc at the time, Dr. Kazutoshi Takahashi were the first to successfully reprogram cells in the lab, producing iPS cells. Their discovery was a major development in what we know about how cells can be reprogrammed.
In 2006, Yamanaka and Takahashi found a way to reprogram adult cells that opened the doors to the further study and treatment of degenerative and genetic diseases, such as Parkinson’s disease. They carried out experiments using combinations of 24 factors to reprogram adult cells to pluripotency. These factors were chosen based on the suggestion that they play a vital role in maintaining embryonic stem cells. They narrowed down the factors to just four –Oct 3/4, Sox2, c-Myc, and Klf4 – and added them to mouse skin cells. The addition of these factors marked the beginning of the reprogramming stages. Over the following two to three weeks, clusters of cells emerged which were of a similar size and shape to ES cells. These new cells were named iPS cells and could be used to make various types of specialised cells including cartilage, heart, and liver cells. Their discovery suggested that iPS cells can be generated from any cell in the body, and won Yamanaka the Nobel Prize for Physiology or Medicine in 2012 along with Professor John Gurdon.
Yamanaka’s group, along with a team in the US, were the first to make human iPS cells in 2007, just one year after their success in mouse cells. Today, scientists can repeat this process to make any type of specialized cell under the right laboratory conditions and this technology is being used to develop new cell therapies. iPS cell therapy has the potential to treat all sorts of diseases and injuries, including anemia, fibromyalgia and spinal cord injuries. Since iPS cells can either be produced from a patient’s own cells or from a healthy donor who is a close genetic match, rejection of the transplanted cells by the immune system should be reduced.
However, there are still questions about the effects reprogramming might have on the cells and how these effects could impact patients. Further research is needed to answer these questions and to develop iPS cells on a large scale that also meet clinical quality and safety guidelines for use in patients.
Access the paper [Cell Press – open access]
Written by Paige Atkins
With thanks to the Center for iPS Cell Research and Application for their assistance.