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Cloned Mice Created from Fully Differentiated Cells


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Research dismisses the notion that adult stem cells are necessary for successful animal cloning, proving instead that cells that have completely evolved to a specific type not only can be used for cloning purposes, but they may be a better and efficient starting point.

As proof, researchers report they created two mouse pups from a type of blood cell that itself is incapable of dividing to produce a second generation of its own kind.

This is the first demonstration that an animal can be derived directly from a fully differentiated cell, report lead researchers Xiangzhong (Jerry) Yang, Ph.D., of the University of Connecticut, and Tao Cheng, M.D., of the University of Pittsburgh, in the journal Nature Genetics.

Moreover, they say results of their studies provide compelling evidence that Dolly the sheep and other mammals cloned by somatic cell nuclear transfer were most likely derived from fully differentiated cells, not adult stem cells, as most have argued in the nine years since Dolly was first created.

Because stem cells have the ability to self-renew and differentiate into any specialized cell type, they have been heralded for their promise for treating a variety of diseases and conditions.

Yet, even for cloning of an embryo to the blastocyst stage, from which embryonic stem cells can be generated, adult stem cells have yielded disappointing results, with success rates in the range of 1 to 5 percent.

Somatic cell nuclear transfer (SCNT), the scientific term for cloning, involves creating an embryo by using a nucleus that's been removed from a somatic cell - any cell other than a reproductive cell - and transferring it into an unfertilized egg that has had its chromosomes removed.

Because the resulting new embryo contains the entire genome of the donor somatic cell it is an identical copy.

This cloned embryo is then implanted into a surrogate mother, and, if the process is successful, is carried to term.

In their studies, the researchers compared the efficiency for cloning mice using a fully differentiated blood cell called a granulocyte with its ancestor cells at different stages: hematopoietic stem cells, which are found in bone marrow and give rise to all red and white blood cells, and progenitor cells.

Granulocytes are well characterized white blood cells unique for their segmented nuclei and the numerous granules in the cells' cytoplasm.

The granulocytes were the efficient donor cells for nuclear transfer among the different lineage cells, with 35 to 39 percent becoming a blastocyst, an early embryo consisting of about 100 to 150 cells, compared to 11 percent for the progenitor.

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