Cells from flakes of skin have grown into living, breeding mice, through a bit of biotechnological wizardry.
This feat helps confirm that reprogrammed adult cells, considered a potentially convenient source of stem cell therapies, share the shape-changing powers of embryonic stem cells.
The goal was to create an animal made entirely from reprogrammed cells, and to confirm that reprogrammed cells “are as good as embryonic stem cells,” said Beijing National Stem Cell Bank director Qi Zhou, co-author of the study published Thursday in Nature.
Much more research is needed to meet the second of Zhou’s criteria, but fulfilling the first is remarkable enough. Just three years ago, it would have been inconceivable.
That’s when Japanese stem cell biologists Shinya Yamanaka and Kazutoshi Takahashi described how four development-regulating genes (carried by viruses into the adult cells of mice) transformed those cells into something very much like an embryonic stem cell.
Embryonic stem cells are able to become any tissue type in the body. Scientists and doctors hope they’ll someday be used to regrow lost limbs and rejuvenate diseased organs. For now, those miracle cures are years, if not decades, away. But even if the cures materialize, embryonic stem cells are difficult to produce. They could end up being rare and expensive.
So when the mouse cell-reprogramming trick was replicated with cells taken from humans, turning skin flakes into brain and bone and muscle cells, scientists rejoiced. A flood of research followed. Hardly a week now goes by without news of improvements to the methods, which tended to result in cancer-prone tissues, or of reprogrammed cells being coaxed into yet another type of tissue.
But at this early date, despite all the progress, many questions still remain. The reprogrammed adult cells, known as induced pluripotent stem cells or iPS cells, are still far more experimental than embryonic stem cells. Their ultimate medical viability is uncertain. It’s not even absolutely clear whether iPS cells can truly become any cell type, or just many of them.
The mice grown by Zhou’s team, described in a study published Thursday in Nature, don’t answer all these questions, but they’re a powerful demonstration of the cells’ flexibility.
“It gives us hope for future therapeutic interventions,” said Fanyi Zheng, a Shanghai Institute of Medical Genetics cell biologist.
Zhou and Zheng’s team reprogrammed mouse skin cells, then injected them into embryos designed to contain double sets of chromosomes. Though these embryos’ original cells couldn’t survive for more than a few days, they provided a jump-start to the reprogrammed cells, which grew as though they were part of a normal embryo.
This test is considered a gold standard of pluripotency: Because the original double-chromosomed cells are doomed, the embryo can only become an adult if the added stem cells turn into every necessary cell type. Embryonic stem cells passed this test a decade ago. Now iPS cells have, too.
From 1,500 engineered embryos, the researchers ended up with 27 mice. The mice have since reproduced, as have their offspring.
“They have shown that iPS cells can satisfy the most stringent criteria of pluripotency,” said George Daley, a Harvard Medical School stem cell biologist who was not involved in the study.
But Daley and other researchers stressed that passing the test doesn’t mean reprogrammed cells and embryonic stem cells are equivalent.
“Here’s another way in which these cells are functionally similar to [embryonic stem cells], but it’s not to say that they’re identical,” said Sean Morrison, director of the University of Michigan’s Center for Stem Cell Biology. There may be things that can only be done with iPS cells, and things that could be done more effectively with embryonic stem cells, he said.
Many researchers also suspect there are subtle differences between reprogrammed cells derived from different sources. A reprogrammed skin cell, for example, may not behave identically to a reprogrammed muscle cell.
“Many questions about the efficiency and fidelity of the process remain,” said Daley.
Zhou and Zheng’s team hasn’t yet analyzed why some embryos succeeded while most failed. Because conducting their experiment with human cells and embryos would be considered immoral, analysis is needed to identify telltale signs of future flaws to determine which human cells are safest for reprogramming.