[Think, now we can study cells known to develop disease and compare
against normal or treatable forms!]
UW-Madison scientists guide human skin cells to embryonic state
Nov. 20, 2007
by Terry Devitt
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 induced cells do all the things embryonic stem cells do. It's
going to completely change the field."
James Thomson, professor of anatomy and the scientist who first
coaxed stem cells from human embryos in 1998
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.
Related audio
Listen to James Thomson's opening statement at the Nov. 21 press
briefing.
Related story
Reprogramming the debate: stem-cell finding alters ethical
controversy
When UW-Madison researchers succeeded in reprogramming skin cells to
behave like embryonic stem cells, they also began to redefine the
political and ethical dynamics of the stem-cell debate, a leading
bioethicist says.
Read more
"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 scientific team from the University of Wisconsin-Madison created
genetic modifications in skin cells to induce the cells into what
scientists call a pluripotent state — a condition that is essentially
the same as that of embryonic stem cells. Junying Yu, James Thomson
and their colleagues introduced a set of four genes into human
fibroblasts, skin cells that are easy to obtain and grow in culture.
High-resultion images related to this story
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,
Jessica Antosiewicz-
all of UW-Madison; and Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir,
Victor Ruotti and Ron Stewart, all of the WiCell Research Institute.
http://www.news.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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