Scientists have moved a step closer toward therapeutic cloning, the strategy of using patients' own cells to treat their diseases. Mice with a Parkinson-like movement disorder showed significant improvement after being implanted with brain cells derived from their own tissue. It's a "technical tour de force," says Harvard stem cell researcher George Daley.
To realize the promise of embryonic stem (ES) cells, scientists say they need to be able to generate batches of cells genetically matched to patients. The best way to do this may be therapeutic cloning, or somatic cell nuclear transfer (SCNT), which involves reprogramming a human egg with DNA from a patient's body cell. No one has yet managed to grow lines of human ES cells through SCNT, although researchers last year reported the first success using monkeys (ScienceNOW, 19 June 2007).
So far, the main advances on the therapeutic cloning front have been with mice. In 2002, scientists successfully regenerated the blood-forming systems in multiple mice with a line of ES-derived cells from a genetically identical mouse. A year later, researchers used cloned cells from mice to treat a mouse model of Parkinson's disease in related animals.
The new study is the first to show that cells from a diseased animal can be used to treat the very same animal. A team led by neuroscientist Lorenz Studer of the Sloan-Kettering Institute in New York City gave mice brain lesions to create a Parkinson-like disorder in which function of the neurotransmitter dopamine was destroyed on one side of their brains. The researchers then performed SCNT, transferring the nucleus of a sick mouse's skin cell into a mouse oocyte from which the nucleus had been removed. These modified cells were grown into early embryos, or blastocysts, which were clones of the afflicted mice. Using the approach, the scientists were able to cultivate 187 embryonic stem cell lines from 24 mice. Many of these cells were cultivated into dopamine-producing neurons. The scientists then grafted these neurons into the brains of the original donors.
The mice with grafts grown from their own cells showed a significant improvement in their ability to control paw movements on the afflicted side. The improvement only occurred when genetically identical neurons were used; when grafted into unrelated mice, most of the cells died, the team reports online this week in Nature Medicine.
"This is a step closer to real cell therapy," says Harvard stem cell researcher Konrad Hochedlinger. Still, Studer notes that the mouse model is a simplified version of Parkinson's disease, so the challenges in treating human patients with therapeutic cloning are still large.
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