Shortcut to making stem cells

2008-10-13 22:21

Washington - Researchers trying to find ways to transform ordinary skin cells into powerful stem cells said on Sunday they found a shortcut by "sprinkling" a chemical onto the cells.

Adding the chemical allowed the team at the Harvard Stem Cell Institute in Massachusetts to use just two genes to transform ordinary human skin cells into more powerful induced pluripotent stem cells or iPS cells.

"This study demonstrates there's a possibility that instead of using genes and viruses to reprogramme cells, one can use chemicals," said Dr Doug Melton, who directed the study published in the journal Nature Biotechnology.

Melton said Danwei Huangfu, a postdoctoral researcher in his lab, developed the new method.

"The exciting thing about Danwei's work is you can see for the first time that you could sprinkle chemicals on cells and make stem cells," Melton, a Howard Hughes Medical Institute Investigator, said in a statement.

Stem cells are the body's master cells, giving rise to all the tissues, organs and blood. Embryonic stem cells are considered the most powerful kinds of stem cells, as they have the potential to give rise to any type of tissue.

Doctors hope to someday use them to transform medicine. Melton, for instance, wants to find a way to regenerate the pancreatic cells destroyed in type 1 diabetes and perhaps cure that disease.

Inserting genes

But pluripotent stem cells such as the embryonic cells are difficult to make, requiring the use of an embryo or cloning technology. Many people also object to their use, and several countries, including the United States, limit funding for such experiments.

In the past year, several teams of scientists have reported finding a handful of genes that can transform ordinary skin cells into iPS cells, which look and act like embryonic stem cells.

To get these genes into the cells, they have had to use retroviruses, which integrate their own genetic material into the cells they infect. This can be dangerous and can cause tumors and perhaps other effects.

Last month US researchers did the same thing using a harmless virus called an adenovirus, but the method was not efficient.

And last week, Shinya Yamanaka of Kyoto University in Japan, who discovered iPS cells in mice, used a loop of genetic material called a plasmid to reformat the cells.

Huangfu tried treating the cells first with valproic acid. After she did this, it only took two of the four usual genes to reprogram the cells into iPS cells, she reported.

This is good because the other two genes usually needed can promote cancer.

Reprogramming

The Melton team used retroviruses to carry the two genes in but suggest they might not be necessary.

"These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical," they wrote in their report.

Huangfu said the valproic acid unravelled the chromatin - the physical structure of the chromosomes - making it possible to get in and alter the DNA more easily.

"We may need two types of chemicals, one to loosen the chromatin structure, and one to reprogramme. We are looking for that reprogramming chemical, and it should be possible to find it eventually," she said.

- Reuters