[tt] Scientists guide human skin cells to embryonic state | Science Blog

[Brian Atkins]

http://www.scienceblog.com/cms/scientists-guide-human-skin-cells-embryonic-state-14847.html

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.

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 James 
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.

http://www.wisc.edu

-- 
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/