Mice cloned from skin cells

Thursday, 15 February, 2007

Healthy and viable mice that survive until adulthood have been cloned from adult stem cells by scientists from Rockefeller University using cells called keratinocyte stem cells.

Keratinocytes come from the skin, making them a particularly attractive stem cell source because of their ready accessibility. One day, they could be used to tailor therapies, as well as to better understand and treat diseases.

Because adult stem cells retain the ability to differentiate into multiple cell types, it has long been expected that they may be better sources of nuclear material for the cloning technique used by Elaine Fuchs, Howard Hughes Medical Institute investigator, and her colleagues, known as nuclear transfer. Fuchs, colleague Peter Mombaerts and their coworkers are the first to successfully and reproducibly clone healthy mice from any type of adult stem cell.

The keratinocyte stem cells used by Fuchs are found in a part of the hair follicle called the bulge. They are involved in hair growth and in repairing skin wounds.

"Researchers have known about these infrequently dividing cells for some time, but only recently have scientists revealed their potential to self-renew and produce multiple types of cells "” the hallmarks of stem cells," Fuchs said.

Keratinocyte stem cells in the bulge have been successfully cultured in the Fuchs' laboratory. When tested in mice, these cells can produce surface skin cells, hair follicles and sebaceous glands.

To clone the mice, researchers removed the nucleus from an unfertilised egg cell, called an oocyte, and replaced it with the nucleus from an adult keratinocyte stem cell. They cultured these hybrid cells in the laboratory to grow them to the blastocyst stage, when the embryo is a tiny hollow ball of cells. At this point, the cultured blastocysts were implanted in a mouse's uterus and allowed to develop into a cloned fetus. This is the cloning technique known as nuclear transfer.

While the new research shows that adult skin stem cells can be a promising starting point for cloning mice, Fuchs said she is more enthusiastic about these cells' potential for generating embryonic stem cells.

Instead of implanting blastocysts and cloning mice, the blastocysts can be cultured in the laboratory to generate embryonic stem cells. In theory, these embryonic stem cells could be coaxed into producing any other type of cell, from neurons to muscle cells to skin cells.

Fuchs said that it is this use of nuclear transfer technology that researchers would like translate to humans. All it would involve, she pointed out, is an unfertilised oocyte, a skin biopsy and a tissue culture dish.

If embryonic stem cells can be generated from a patient's skin, and then used to create cells or tissues according to the patient's specific need, the problem of immune rejection might be avoided.

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