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The Real Stem Cell Hope

Cloned stem cells could offer a clearer window on diseases.
February 8, 2006

When Korean stem cell researcher Woo-suk Hwang announced in 2005 that he had cloned 11 lines of patient-specific stem cells, the research community cheered. Media reports proclaimed that the feat would open up the world of stem cell transplants. But many scientists were excited for another reason: it meant they had a whole new toolbox to study human disease. Researchers could now search for new drug targets or test new therapies in a cell model that was potentially much more accurate than the standard tools.

No one has yet achieved this feat – Hwang’s stem cell lines turned out to be a fraud (see “Stem Cell Uncertainty”). But in the wake of that scandal, other researchers are revving up their efforts to create cloned stem cells. They say that, although cell transplants are an exciting possibility, a more immediate use for these cells will be as models to study human disease.

“You could make a stem cell line that has ALS or Parkinson’s, using DNA from a patient that really has the symptoms,” says Evan Snyder, director of the stem cells and regeneration program at the Burnham Institute in La Jolla, CA.

All existing stem cell lines were created from human embryos. Scientists can study how these cells develop into different cell types; but because researchers don’t know anything about the people who donated the eggs and sperm, they can’t link the behavior of the cells to a particular disease.

To create a cloned stem cell, scientists take the DNA from a human skin cell and insert it into an egg that has had its own DNA removed. The egg then starts dividing, and scientists can harvest stem cells a few days later. Because the cells would be genetically identical to the patient whose DNA was used to create the cell, they will undergo some of the same molecular changes that underlie that patient’s disease.

Scientists can coax the cells to develop into the cell type damaged in a disease, such as dopamine neurons in Parkinson’s or insulin-producing cells in diabetes, and study the progression of the disease and the best ways to treat it.

“Very often the animal models that exist for a particular disease really don’t authentically replicate what’s going on in a human,” says Snyder. “So if we have a treatment for mice, we don’t know if that will translate to treatment for humans.”

Unlike in most animal models, one of the major advantages of cloned stem cells is that scientists don’t need to know the exact genetic changes that underlie a particular disease, says Kevin Eggan, assistant professor of molecular and cellular biology at Harvard University, who plans to start human therapeutic cloning experiments as soon as he gets regulatory approval to study neurodegenerative diseases. These cells could be used to look for compounds and other factors that slow down or speed up the progression of the disease, he says. “You can replay development in the dish over and over under different environmental conditions.”

Scientists could also use cloned stem cell lines to create new diagnostic tests or tools for drug discovery. “We have nothing in the genetic tool box to diagnose what’s happening early on in a disease,” says Renee A. Reijo Pera, codirector of the human stem cell biology program at the University of California, San Francisco. “Embryonic stem cells let you go back to day-one of the disease.”

In Alzheimer’s disease, for example, the brain is significantly damaged by the time the patient sees a doctor. To search for early signs of the disorder, scientists could generate stem cells using DNA from an Alzheimer’s patient, then coax those cells to differentiate into neurons, monitoring the cells for specific proteins or other molecular changes that are different from neurons derived from healthy embryonic stem cells. The same approach might work with cancer, which is characterized by a series of harmful genetic changes. “We want to know what’s the earliest you can detect differences in disease cells,” says Reijo Pera, who is planning a new research program in human therapeutic cloning.

Scientists also hope that cloning stem cells will bring the field one step closer to a major goal of stem cell biology: to take an adult cell and turn it back into a stem cell without the use of human eggs. This feat would ultimately circumvent the biggest ethical concerns surrounding therapeutic cloning – the creation and destruction of a human embryo. Scientists hope that if they can understand how an egg “reprograms” an adult cell into its undifferentiated state, they can eventually eliminate the need for human eggs and embryos.

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