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"Organ Regeneration's a Snap!" Said Seth

As I made one of my many daily visits to the NY Times homepage, I found this article by Nicholas Wade about organ regeneration. To say the discovery of being able to regrow cells is big would be an understatement, so I'm doing my best to make sure the public is aware of such a medical advancement that could, and likely will change the face of medical science.

If this procedure is successful and accepted, it very well could affect almost everyone. Think of the possibilites of being able to quickly and effectively regenerate cells, hearts, lungs, etc.? With the way human and their bodily processes are developing and responding to our changing world it's happening more and more that viruses and cancers are unsettelingly prevelent. But, the ability to regrow healthy cells could mean a lot for treatments, and it will finally be a relieft to be able to research this ability without ethical issues being raised. This is crazy and interesting stuff here kiddos, but we should all know about it.


In a surprising advance that sidesteps the ethical debates surrounding stem cell biology, researchers have come much closer to a major goal of regenerative medicine, the conversion of a patient’s cells into specialized tissues that might replace those lost to disease.

The advance is an easy-to-use technique for reprogramming a skin cell of a mouse back to the embryonic state. Embryonic cells can be induced in the laboratory to develop into many of the body’s major tissues.

If the technique can be adapted to human cells, it would let scientists use a patient’s skin cell to generate new heart, liver or kidney cells that might be transplantable and would not be rejected by the patient’s immune system.

Previously, the only way scientists knew they were likely to get such cells is by nuclear transfer, the insertion of an adult cell’s nucleus into an egg whose own nucleus has been removed. The egg somehow reprograms the nucleus back to embryonic state.

The new technique, developed by Shinya Yamanaka of Kyoto University, depends on inserting just four genes into a skin cell. These accomplish the same reprogramming task as the egg, or at least one very similar.

The technique is much easier to apply than nuclear transfer, does not involve the expensive and controversial use of human eggs, and should avoid all or almost all of the ethical criticism directed at the use of embryonic stem cells.

“From the point of view of moving biomedicine and regenerative medicine faster, this is about as big a deal as you could imagine,” said Irving Weissman, a leading stem cell biologist at Stanford University.

David Scadden, a stem cell biologist at the Harvard Medical School, said the finding that cells could be reprogrammed with simple biochemical techniques “is truly extraordinary and frankly something most assumed would take a decade to work out.”

The new technique seems likely to be welcomed by many who have opposed human embryonic stem cell research. It “raises no serious moral problem, because it creates embryonic-like stem cells without creating, harming or destroying human lives at any stage,” said Richard Doerflinger, a spokesman on stem cell issues for the United States Conference of Catholic Bishops. In themselves, embryonic stem cells “have no moral status,” and the bishops’ objections to embryonic stem cell research rest solely on the fact that human embryos must be harmed or destroyed to obtain them, he said.

Ronald Green, an ethicist at Dartmouth College, said it would be “very hard for people to say that what is created here is a nascent form of human life that should be protected.” The new technique, if adaptable to human cells, “will be one way this debate could end,” he said.

Ever since the creation of Dolly, the first cloned mammal, scientists have sought to lay hands on the mysterious chemicals with which an egg will reprogram a mature cell nucleus injected into it and set the cell on the same path of embryonic development as when egg and sperm combine.

Years of patient research have identified many of the genes that are active in the embryonic cell and maintain its pluripotency, or ability to morph into many different tissues. Last year Dr. Yamanaka and his colleague Kazutoshi Takahashi, both at Kyoto University, published a remarkable report relating how they had guessed at 24 genes that seemed responsible for maintaining pluripotency in mouse embryonic stem cells.

When they inserted all 24 genes into mouse skin cells, the cells showed signs of pluripotency. The Kyoto team then subtracted genes one by one until they had a set of four genes that were essential. The genes are inserted into viruses that infect the cell and become active as the virus replicates. The skin cell’s own copies of these genes are repressed since they would interfere with its function. “We were very surprised” that just four genes are sufficient to reprogram the skin cells, Dr. Yamanaka said.

Dr. Yamanaka’s report riveted the attention of biologists elsewhere. Two teams set out to repeat and extend his findings, one led by Rudolf Jaenisch of the Whitehead Institute and the other by Kathrin Plath of the University of California, Los Angeles, and Konrad Hochedlinger of the Massachussetts General Hospital. Dr. Yamanaka, too, set about refining his work.

In articles being published in Nature and a new journal, Cell-Stem Cell, the three teams show that injection of the four genes identified by Dr. Yamanaka can make mouse cells revert to cells that are indistinguishable from embryonic stem cells. Dr. Yamanaka’s report of last year showed that only some properties of embryonic stem cells were attained.

This clear confirmation of Dr. Yamanaka’s recipe is exciting to researchers because it throws open to study the key process of multicellular organisms, that of committing cells to a variety of different roles, even though all carry the same genetic information.

Recent studies have shown that the chromatin, the complex protein material that clads the DNA in chromosomes, is not passive packaging material but highly dynamic. It contains systems of switches that close down large suites of genes but allow others to be active, depending on the role each cell is assigned to perform.

Dr. Yamanaka’s four genes evidently reset the switch settings appropriate for a skin cell to ones that specify an embryonic stem cell. The technique is easy to use and “should revolutionize the field since every small lab can work on reprogramming,” said Alexander Meissner, a co-author of Dr. Jaenisch’s report.

An immediate issue is whether the technique can be reinvented for human cells. One problem is that the mice have to be interbred. Another is that the cells must be infected with the gene-carrying virus, which is not ideal for cells to be used in therapy. A third issue is that two of the genes in the recipe can cause cancer. Indeed 20 percent of Dr. Yamanaka’s mice died of the disease. Nonetheless, several biologists expressed confidence that all these difficulties will be sidestepped somehow.

“The technical problems seem approachable — I don’t see anyone running into a brick wall,” said Owen Witte, a stem cell biologist at the University of California, Los Angeles. In a Web cast about the research, Dr. Jaenisch predicted that the problems of adapting the technique to human cells will be solvable but he did not know when.

If a human version of Dr. Yamanaka’s recipe is developed, one important research use, Dr. Weissman said, will be to reprogram diseased cells from patients so as to study the molecular basis of how their disease develops.

Beyond that is the hope of generating cells for therapy. Researchers have learned how to make embryonic cells in the laboratory develop into neurons, heart muscle cells and other tissues. In principle these might be injected into a patient to replace or supplement the cells of the diseased tissue, without fear of immune rejection. No one really knows if the new cells would succumb to the same disease process, or if they would be well behaved, given that they developed in a laboratory dish without recapitulating the exact succession of environments they would have experienced in the embryo.

Still, repairing the body with its own cells should in principle be a superior form of medicine to the surgeon’s knife and the oncologists’ poisons.

But the first fruit of the new technique will be in figuring out how cells work.

This and other methods will lead to an explosion of information that will “open the door for understanding how cells program and re-program their fate,” Dr. Scadden predicted. If and when applicable to human cells, he said, the four-gene approach “will have profound implications for new biology, regenerative medicine and will change the ethical debate around stem cells.”

 

Seth Plattner
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