Mouse, Heal Thyself: Therapeutic cloning from a mouse’s own cells

Scientists have treated mice that have a Parkinson’s disease–like condition by making new neurons from each mouse’s own skin cells.

The work demonstrates the potential of therapeutic cloning for replacing damaged neurons in people who have Parkinson’s.

The individual steps of the process have each been done before in mice: cloning skin cells to make early embryos, extracting stem cells from the embryos, converting these embryonic stem cells into the right kind of nerve cells, and implanting the nerve cells into the mouse brains.

But the new study is the first to put all the pieces together by extracting skin cells from the same mouse that ultimately will receive the newly minted nerve cells, mimicking one procedure that scientists have proposed for treating Parkinson’s disease in people.

“Nobody had ever done it,” says Viviane Tabar of the Sloan-Kettering Institute in New York City.

In previous studies, groups of mice all received nerve cells derived from a single mouse. Preventing the bodies of the recipient mice from rejecting the foreign cells required impairing the animals’ immune systems or using inbred mice.

“It’s easy just to say we need to use an individual’s own cells when you haven’t shown that it’s any better or that it’s even feasible,” says Tabar. “We were able to demonstrate that [self-derived] tissue worked much better functionally and immune-wise.”

Tabar’s team treated one group of mice with the new method. Each mouse received nerve cells made from skin cells taken from its own tail. Another group of mice all received foreign cells. As expected, the genetically matched nerve cells took up residence in each mouse’s brain and were thriving 11 weeks after implantation. But in the other group, few nerve cells survived, presumably because of rejection by the immune system, the researchers report online March 23 in Nature Medicine.

In principle, the body should accept genetically matched cells, but the implanted nerve cells had gone through a lot of manipulation that could have caused complications. First, cloning experts at the RIKEN Center for Developmental Biology in Kobe, Japan, cloned each mouse’s skin cells, which involved a jolt of chemicals. Then Tabar’s team exposed the resulting embryonic stem cells to a mixture of signaling molecules to steer the stem cells toward becoming neurons.

“You take the cells out and you put them back and you don’t know what’s happening in between,” comments Kai-Christian Sonntag of the Center for Neuroregeneration Research at Harvard Medical School in Belmont, Mass. The cloning and conversion to nerve cells “might have changed the cells’ immune profiles, and they might have gotten rejected. You never know until you have proven it.”

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