A group of scientists from the US and Germany have achieved what has been heralded as a breakthrough in stem cell research and development: they have found a way of making embryonic-like stem cells by reprogramming adult cells without having to alter them genetically, a process that has been linked to the development of cancerous tumors.

The study was led by Associate Professor Sheng Ding, from the The Scripps Research Institute, at La Jolla, California, and colleagues, and is published in an advance, online issue of the journal Cell Stem Cell on 23 April 2009.

“We are very excited about this breakthrough in generating embryonic-like cells from fibroblasts [cells that gives rise to connective tissue] without using any genetic material,” said Ding.

“Scientists have been dreaming about this for years,” he added.

Stem cells are master cells: they can become nearly any cell of the body. Embryonic stem cells are the “best”, in that they can really become any other cell, whereas other types of stem cell have a wide range of possibilities but not as wide as the embryonic stem cell.

The holy grail of stem cell research is to to make and use stem cells to replace diseased and damaged cells that will not regenerate themselves naturally, such as the pancreatic cells that make insulin and the dopamine producing brain cells that are damaged by Parkinson’s disease. Another potential application would be to make new organs, which might not only help reduce transplant waiting lists, but also reduce transplant failures due to rejection of donor tissue, since the new organs would be made from patients’ own cells.

The first breakthrough on this journey came a few years ago when a team of scientists in Japan turned mouse skin cells in mouse stem cells by inserting four genes into the skin cells, causing them to revert to a more primitive type of cell that is somewhat like an embryonic stem cell in that it has the potential to become almost any type of cell in the body (the so-called induced pluripotent stem cell, or iPS cell). The genes worked by manipulating the behaviour of other genes.

However, a big problem with inserting genes into cellular DNA as a way to reprogram cells is that it changes the DNA which is then passed on in any new cells, and stays there. Thus the new cells carry an unknown risk, in that nobody really knows (because we haven’t had enough years to look at long term effects) what impact this might have in the long run, and, also in the case of these four genes in particular, research has linked them with the growth of cancerous tumors.

So the ideal would be to find a way to reprogram cells to become iPS cells without having to disturb their DNA. This is what Ding and colleagues achieved: they engineered and used recombinant proteins, scraps of DNA from different organisms, that manipulated the behaviour of the genes in fibroblast mouse cells so that they reverted to embronic-like stem cells. They called them “piPS” cells, short for protein induced pluripotent stem cells. Recombinant proteins are already used in drugs to treat diseases.

They also found that the piPS from fibroblasts behaved no differently to embryonic stem cells and differentiated into various cell types, including beating heart muscle, cardiac muscle cells, neurons and pancreatic cells.

“Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins.”
Hongyan Zhou, Shili Wu, Jin Young Joo, Saiyong Zhu, Dong Wook Han, Tongxiang Lin, Sunia Trauger, Geoffery Bien, Susan Yao, Yong Zhu, Gary Siuzdak, Hans R. Schöler, Lingxun Duan, Sheng Ding.
Cell Stem Cell, 23 April 2009
doi:10.1016/j.stem.2009.04.005

Additional Sources: The Scripps Research Institute.

Written by: Catharine Paddock, PhD