Scientists Guide Human Skin Cells To Embryonic State

[Guest guest]

Scientists Guide Human Skin Cells To Embryonic State

In a paper to be published Nov. 22 in the online edition of the

journal Science, a team of University of Wisconsin-Madison

researchers reports the genetic reprogramming of human skin cells to

create cells indistinguishable from embryonic stem cells.

http://www.sciencedaily.com/releases/2007/11/071120092709.htm

The finding is not only a critical scientific accomplishment, but

potentially remakes the tumultuous political and ethical landscape

of stem cell biology as human embryos may no longer be needed to

obtain the blank slate stem cells capable of becoming any of the 220

types of cells in the human body. Perfected, the new technique would

bring stem cells within easy reach of many more scientists as they

could be easily made in labs of moderate sophistication, and without

the ethical and legal constraints that now hamper their use by

scientists.

The new study was conducted in the laboratory of UW-Madison

biologist Thomson, the scientist who first coaxed stem cells

from human embryos in 1998. It was led by Junying Yu of the Genome

Center of Wisconsin and the Wisconsin National Primate Research

Center.

" The induced cells do all the things embryonic stem cells do, "

explains Thomson, a professor of anatomy in the University of

Wisconsin School of Medicine and Public Health. " It's going to

completely change the field. "

In addition to exorcising the ethical and political dimensions of

the stem cell debate, the advantage of using reprogrammed skin cells

is that any cells developed for therapeutic purposes can be

customized to the patient.

" They are probably more clinically relevant than embryonic stem

cells, " Thomson explains. " Immune rejection should not be a problem

using these cells. "

An important caveat, Thomson notes, is that more study of the newly-

made cells is required to ensure that the " cells do not differ from

embryonic stem cells in a clinically significant or unexpected way,

so it is hardly time to discontinue embryonic stem cell research. "

The successful isolation and culturing of human embryonic stem cells

in 1998 sparked a huge amount of scientific and public interest, as

stem cells are capable of becoming any of the cells or tissues that

make up the human body.

The potential for transplant medicine was immediately recognized, as

was their promise as a window to the earliest stages of human

development, and for novel drug discovery schemes. The capacity to

generate cells that could be used to treat diseases such as

Parkinson's, diabetes and spinal cord injuries, among others,

garnered much interest by patients and patient advocacy groups.

But embryonic stem cells also sparked significant controversy as

embryos were destroyed in the process of obtaining them, and they

became a potent national political issue beginning with the 2000

presidential campaign. Since 2001, a national policy has permitted

only limited use of some embryonic stem cell lines by scientists

receiving public funding.

In the new study, to induce the skin cells to what scientists call a

pluripotent state, a condition that is essentially the same as that

of embryonic stem cells, Yu, Thomson and their colleagues introduced

a set of four genes into human fibroblasts, skin cells that are easy

to obtain and grow in culture.

Finding a combination of genes capable of transforming

differentiated skin cells to undifferentiated stem cells helps

resolve a critical question posed by Dolly, the famous sheep cloned

in 1996. Dolly was the result of the nucleus of an adult cell

transferred to an oocyte, an unfertilized egg. An unknown

combination of factors in the egg caused the adult cell nucleus to

be reprogrammed and, when implanted in a surrogate mother, develop

into a fully formed animal.

The new study by Yu and Thomson reveal some of those genetic

factors. The ability to reprogram human cells through well defined

factors would permit the generation of patient-specific stem cell

lines without use of the cloning techniques employed by the creators

of Dolly.

" These are embryonic stem cell-specific genes which we identified

through a combinatorial screen, " Thomson says. " Getting rid of the

oocyte means that any lab with standard molecular biology can do

reprogramming without difficulty to obtain oocytes. "

Although Thomson is encouraged that the new cells will speed new

cell-based therapies to treat disease, more work is required, he

says, to refine the techniques through which the cells were

generated to prevent the incorporation of the introduced genes into

the genome of the cells. In addition, to ensure their safety for

therapy, methods to remove the vectors, the viruses used to ferry

the genes into the skin cells, need to be developed.

Using the new reprogramming techniques, the Wisconsin group has

developed eight new stem cell lines. As of the writing of the new

Science paper, which will appear in the Dec. 21, 2007 print edition

of the journal Science, some of the new cell lines have been growing

continuously in culture for as long as 22 weeks.

The new work was funded by grants from the Charlotte Geyer

Foundation and the National Institutes of Health. In addition to Yu

and Thomson, authors of the new study include Maxim A. Vodyanik, Kim

Smuga-Otto, Antosiewicz-Bourget, L. Frane and Igor

I. Slukvin, all of UW-Madison; and Shulan Tian, Jeff Nie, Gudrun A.

Jonsdottir, Victor Ruotti and Ron , all of the WiCell

Research Institute.