Therapeutic cloning creates perfect match
nature.com
Animal-specific stem cells treat Parkinson's symptoms in mice.
Heidi Ledford
Researchers have used therapeutic cloning to transform a mouse's tail cells into ones that can treat it for disease. The study helps advance the prospect of creating cell lines perfectly matched to human patients.
In therapeutic cloning — also called somatic-cell nuclear transfer — researchers transplant the nucleus from an adult cell into an egg whose own nucleus has been removed. The eggs are used to grow embryonic stem cells, which are then coaxed to form a desired cell type. In this case, the stem cells were differentiated into nerve cells producing the neurotransmitter dopamine. These cells are damaged in patients with Parkinson’s disease, resulting in tremors and loss of muscle control.
The process is laborious and technically challenging. Previous work had shown that dopamine-producing cells formed from embryonic stem cells could be transplanted into mice with a model of Parkinson’s disease1. The transplants successfully relieved symptoms, but in that case the researchers derived the stem cell line from a different (but genetically related) donor, not from the mouse that was being treated.
Therapeutic first
The new study is the first to take cells from a mouse, transform them through therapeutic cloning into a new cell line, and use this to treat the original donor.
The technique is still a long way from application in humans, but does advance the field toward that ultimate goal, observers say. “It’s the next iterative step in the process of showing that nuclear transfer may be a reasonable way of finding patient-specific stem cell lines,” says Evan Snyder, a stem cell researcher at the Burnham Institute for Medical Research in San Diego, California, who was not involved with the work.
Deriving stem cell lines from embryos remains a very inefficient process. The researchers report in Nature Medicine that they generated 187 different lines from 5,099 eggs — an efficiency of nearly 4%2. After the mice received the animal-specific stem cells, they showed signs of neurological improvement within three weeks.
In contrast, transplanted cells derived from unrelated mice often failed to survive in their new hosts. Mice that received those cells showed signs of inflammation in the brain. “This is clearly not something you want,” says Lorenz Studer, a member of the team at the Memorial Sloan-Kettering Cancer Center in New York.
Next steps
The grafted cells also sometimes yielded an overgrowth of undifferentiated cells, probably because other cell types were inadvertently transplanted into the mice along with the nerve cells. An important next step, says Viviane Tabar, a neurobiologist at Memorial Sloan-Kettering Cancer Center and lead author of the paper, is to better purify dopamine-producing cells before performing the transplant. “This is going to be an issue that needs to be dealt with,” agrees Snyder.
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There has been recent speculation that therapeutic cloning may one day be abandoned in favour of a new technique that creates cells similar to embryonic stem cells, called induced pluripotent stem (iPS) cells. In this method, adult cells are genetically reprogrammed to revert to an embryonic-like state by insertion of just a few genes. “Nuclear transfer is a very technically complex and time consuming process,” says Snyder. “The subtext that everybody is reading into this is, now that we have reprogramming, who cares?”
But methods for creating iPS cells are also inefficient, Snyder notes, and the technique is still poorly understood. So Snyder says it is important to continue optimizing therapeutic cloning techniques, because it is not yet clear which method will produce cell lines best suited for clinical application. “We still need to pursue this kind of work,” he says. "All of these methods still need to be compared, head to head."
References
1. Barberi, T. et al. Nat. Biotechnol. 21, 1200–1207 (2003).
2. Tabar, V. et al. Nat. Med. doi:10.1038/nm1732 (2008). |
