Scientists Reprogram Cells Without Cloning

WASHINGTON (Reuters) - Scientists said on Tuesday they had transformed ordinary human skin cells into immune cells in an experiment that, if it can be repeated, might bypass the need for either stem cells or highly controversial cloning technology for many medical therapies.

The team at biotech start-up Nucleotech LLC hope to be able to offer patients grow-your-own transplants that could theoretically be used to treat diseases such as immune deficiencies and juvenile diabetes.

Many teams are working on the idea, but nearly all had assumed the need for stem cells, the body's master cells, which are elusive and difficult to grow in the lab. They can be found in blood and tissue, or can be taken from embryos -- usually obtained from fertility clinics.

Such stem cells could also theoretically be made using cloning technology -- something highly controversial and the subject of competing legislation in the U.S. Congress. President Bush supports a complete ban on the use of cloning technology involving humans.

A coalition of senators introduced a new bill on Tuesday that would specifically allow the use of cloning technology in medical research but ban it for the purposes of making a baby.

James Robl, Philippe Collas and colleagues at Nucleotech and the University of Oslo believe they have found a way around the controversy.

By punching holes in mature skin cells and soaking them in a solution made from immune system cells, they said, they turned them into what look like T-cells -- key immune system cells.

Robl, a leading stem-cell researcher who left the academic world to work for biotechnology companies, wants to use the approach to transform medicine.

"It would be a one-day procedure, in principle," he said. "The patient would come in and give a skin biopsy to the lab to reprogram and the day after you could put the cells back into the patient."

Researchers working with stem cells have had a similar idea for treating diabetes by making pancreatic cells, for treating Parkinson's or Alzheimer's by making new brain cells and for treating spinal cord injuries by making new nerve cells.

Making T-cells could have immediate applications in treating cancer, said Collas, who led the study. A patient's skin cells could be transformed into T-cells that would recognize and attack the patient's own tumor.

The company was also looking at making pancreatic islet cells -- the cells that make insulin and which are destroyed in juvenile or type-I diabetes, Robl added.

Writing in the journal Nature Biotechnology, the team said they made the skin cells permeable by punching tiny pores in the cell walls. They then grew them in a solution containing extracts from T-cells.

The new cells stopped expressing the genes that skin cells express -- meaning they stopped functioning like skin cells, and instead turned on genes usually active only in immune cells, such as IL2, IL7, CD3, CD4 and RANTES.

"In effect you are washing regulatory factors out from inside the cell and replacing them," Robl said.

Instead of harnessing an early stem cell whose genes have not yet been all turned on, the team completely changed the cell's environment and thus changed the cell's function.

Although Robl hopes the technology will rival stem-cell and cloning approaches, both he and Collas oppose restriction of any kind on such research.

Dr. Irving Weissman of Stanford University, a supporter of cloning and stem-cell research, said he had not seen the study but added, "I would be highly skeptical."

Others agreed with Robl that all techniques need to be explored. "There is so much that we don't know," Donald Coffey, a specialist in cancer and molecular biology at Johns Hopkins University in Baltimore, said in an interview. "I say let all flowers bloom."

In a commentary in Nature Biotechnology, Azim Surani and Patrick Western of Cambridge University in Britain said it looked to them as if the cells had only been partially reprogrammed but said Collas had come up with a "potentially powerful system" for studying cell biology.

Christian radio is reporting on the lie of this new campaign and effort of the Dem. Senate to call "therapeutic" cloning someting other than cloning. Their PR campaign, "Cure Now!" includes TV ads stating that those who oppose "therapeutic" cloning are against the cure for diabetes and cancer...even though the only real progress has been with adult stem cells...not these created Mengele cells...and the Senate's Bill will take money from known cures using these adult stem cells for a handful of magic beans, a possibility unproven by years of research, as ethereal as cold fusion and as close to reality. It's a sham, a cruel hoax. Shame on the Democrats.

In effect you are washing regulatory factors out from inside the cell and replacing them

Can anyone with a bio/chem/Med background elaborate on what these regulatory factors are? Enzymes, proteins, etc? Would these factors be at all related to the 'chaparone proteins' I recently read about- the ones responsible for making sure newly produced proteins are correctly folded? And finally, how much of this information is actually in the DNA?

"Transcription factors" are proteins which activate or repress the transcription of genes by glomming onto control sequences adjacent to the genes. Every different type of cell has a different pattern of gene expression; the set of genes which is expressed is determined by the set of transcription factors present in the cell, which is itself the end result of previous gene expression. Development involves the turning on and off of genes in different patterns, like Christmas tree lights, as the cells multiply and migrate during the formation of the embryo. Ultimately, these sequenced patterns of expression are encoded by the DNA, although in a much less direct way than the manner in which the genes codes for proteins.

You might reasonably ask how the cells of the body can end up taking on different fates, given that they all contain the same DNA program. The fertilized egg is not perfectly symmetrical -- when it divides for the first time, the contents of the two daughter cells are already different, and this immediately leads to differences in gene expression. As the cells divide, the program of development leverages other, random symmetry-breaking events to sub-divide the embryo into fields of cells of different types, leading to the formation of the body plan and the various organs and distinct tissues of the adult.

The molecular chaperones you mention are used in many different cellular processes, and are not directly related to "transcription factors."

There is an excellent "cartoon" introduction to gene regulation at CodeGrok.

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