Researchers learn to reprogram cells

Recent discoveries at UCLA indicate the possibility of reprogramming normal tissue cells to have the same characteristics of embryonic stem cells.

Researchers at the UCLA Institute of Stem Cell Biology and Medicine were able to turn a specific type of mouse cell into a cell that is identical to an embryonic stem cell by adding four factors, the results of which have been published today in the journal Cell Stem Cell.

With much controversy surrounding the use of embryonic stem cells for scientific research since it requires the destruction of a human embryo, this discovery can lead to a solution, as it eliminates the need to use embryos, said James Battey, vice chair of the National Institutes of Health’s stem cell task force.

Embryonic stem cells are important because they are unspecialized and pluripotent, or able to develop into any type of adult cell. The process of developing into a specific cell type is called differentiation.

Yet the research conducted at the institute deals with the opposite process, in which an already-differentiated and fixed adult cell is reprogrammed to form the pluripotent cell, Battey said.

“It is the differentiation process but in reverse,” he said. “(Some refer to it as) turning back time.”

Four transcription factors, a type of protein, are added to normal adult cells, giving the cells the same function and structure as stem cells, with the same unlimited capacities to form many different cell types.

“We’ve run many tests and in every one of them, we couldn’t find any difference between embryonic stem cells and reprogrammed cells,” said Kathrin Plath, an assistant professor of biological chemistry and coauthor of the study.

These reprogrammed cells can then be used for therapeutic medicine because they can differentiate into different cells in the body.

The cells could be used to generate neurons to repair spinal cord injuries or Parkinson’s disease, to generate cell types to treat disorders such as diabetes, or a variety of other options, said Amander Clark, an assistant professor of molecular, cell, and developmental biology.

“There’s the potential to become any part of the body,” Clark said. “You can even make an entire mouse from a single stem cell.”

The study at the institute was started after Japanese researcher Shinya Yamanaka identified the four factors last year, but he was only able to partially reprogram the cells to form embryonic stem cells because they couldn’t grow into live animals.

“Yamanaka’s research was absolutely critical in showing that one can derive embryonic cells back from adult cells,” Battey said.

Despite the key finding of fully reprogramming a certain type of mouse cell called fibroblast, research still needs to be conducted with human cells before they are used for human medicine.

“There are obviously differences in cells from mice and from humans,” Plath said. “The transcription factors may be entirely different or possibly the same.”

She said it could be anywhere from a few months to five to 10 years, depending on whether the transcription factors in mice are the same in humans, before results are obtained for human cells.

Another major problem the lab is currently working on is finding a way to introduce the cells without any risks.

Currently, the process involves introducing an oncogene, a potent cause of cancer, into the mouse gene. Though it is usually silenced during gene expression, it can easily be reactivated and lead to tumor growth, Battey said.

“The goal right now is to duplicate the results without the risk factor,” he said.

Plath is currently exploring the possibility of introducing a factor, such as a protein or virus, that doesn’t integrate into the gene but can still have the same effect.

Further information about the mechanism by which the transcription factors work is also being researched.

Though there are many aspects that need to be worked out, the successful reprogramming of mouse fibroblast cells by adding the four transcription factors is a significant step forward in science, Battey said.

“This is a major breakthrough and will no doubt attract attention,” he said.