Monday, August 3, 2009

Health

Scripps lab creates adult mice from mouse skin cell; advances stem cell research


Which came first, the mouse or the egg? For once, the age-old riddle is easy to solve.
Today, it's the mouse.

Scientists at The Scripps Research Institute have created healthy adult mice out of mouse skin cells - no sperm, no egg. Just skin.
The feat, described in the scientific journal Nature on Monday, was intended to prove that adult cells can be reprogrammed backwards in their development, until they have all the desirable characteristics of embryonic stem cells. Two Chinese groups reported the same findings on Monday, using slightly different methods.
Observers said it was both remarkable and promising news for the future of stem cell research.
"We can take a cell from our hand and make a fetus. I mean that's astounding," said professor Gerard McGill, a medical ethicist at Duquesne University 's Center for Healthcare Ethics.
But more than that, McGill said, it means the ability to treat diabetes, Alzheimer's, Parkinson's, hearing loss, or spinal cord damage with a patient's own cells is within reach. Medically, infusing a patient with his own heart stem cells to repair diseased tissue would be preferable to infusing that patient with someone else's cells, because of the risk of rejection.
And no embryos need be destroyed to accomplish the cures.
"It proves that reprogrammed cells are equivalent to embryonic stem cells," McGill said. "Treatments are at least 15 or 20 years away, but they are reasonable."
The research took place at Scripps' La Jolla campus, but it was funded, in part, with grants from two Palm Beach foundations, the Whitehall Foundation and the O'Keeffe family.
"This is quite an exciting area to us, to think you can actually cure someone with diabetes and do it with their own cells," said Clare O'Keeffe, of Palm Beach. Her family's gift is supporting the salaries of several graduate students working in the La Jolla research lab, said Scripps cell biologist Kristin Baldwin.
The work validated three-year-old findings from Kyoto University's Shinya Yamanaka. The gold standard for proof that adult cells could be as useful as embryonic cells was to show that they could make a completely healthy embryo, scientists agreed.
Many scientists have tried, but until now were unable to produce viable, living mice, Baldwin said.
The protocols developed by the Scripps group resulted in successful adults 13 percent of the time. The Chinese groups' success rate was significantly lower, she said.
"We don't know which of the protocol changes we implemented are required," she said. Baldwin said she's not certain which element of her team's methods made the difference. The research continues.
Reprogramming mouse skin cells to grow into complete mice required a decade's worth of advances in mouse genetics, genetic engineering, stem cell biology and reproductive technology.
The scientists started using a standard cell-type used by other labs - fetal mouse skin cells.
They then genetically engineered viruses to carry genes for four key proteins believed to be able to reprogram the cell's behavior. The viruses infected the skin cells, forcing them to produce the compounds.
The scientists hand-selected cells that had the most obvious stem-cell like traits.
Genes inserted into the cells enabled the scientists to turn off the embryonic reprogramming factors when they were no longer desired.
The cells were cultivated in nutrients and eventually transferred into fertile female mice. Two of the embryos survived to become fertile adults.
"Now we need to ask how normal are these mice and their cells," she said.
Today, the progeny of the skin-derived mice continue to live in air-conditioned comfort in La Jolla, she said.
"They live a very cushy life in our animal facility, where they are extremely well cared for," Baldwin said.

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