New Technique Produces Genetically Identical Stem Cells

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New Technique Produces Genetically Identical Stem Cells

http://www.medicalnewstoday.com/articles/113621.php

Adult cells of mice created from genetically reprogrammed cells - so-

called induced pluripotent stem (IPS) stem cells - can be triggered

via drug to enter an embryonic-stem-cell-like state, without the need

for further genetic alteration.

The discovery, which promises to bring new efficiencies to embryonic

stem cell research, is reported in the July 1, 2008, online issue of

Nature Biotechnology.

" This technical advancement will allow thousands of identical

reprogrammed cells to be used in experiments, " says Marius Wernig,

one of the paper's two lead authors and a postdoctoral researcher in

Whitehead Member Rudolf Jaenisch's lab.

" Using these cells could help define the milestones of how cells are

reprogrammed and screen for drug-like molecules that replace the

potentially cancer-causing viruses used for reprogramming, " adds

Lengner, the other lead author and also a postdoctoral

researcher in the Jaenisch's lab.

In the current work, Wernig and Lengner made mice created in part

from the embryonic-stem-cell-like cells known as IPS cells. The IPS

cells were created by reprogramming adult skin cells using

lentiviruses to randomly insert four genes (Oct4, Sox2, c-Myc and

Klf4) into the cells' DNA. The IPS cells also were modified to switch

on these four genes when a drug trigger, doxycycline, is added to the

cells.

Wernig and Lengner then took cells from each IPS mouse and introduced

the doxycycline trigger, thereby changing the adult mouse cells into

IPS cells.

While earlier reprogramming experiments have typically induced

pluripotency in adult skin cells, Wernig and Lengner were able to

employ this novel method to successfully reprogram multiple cell and

tissue types, including cells of the intestine, brain, muscle,

kidney, adrenal gland, and bone marrow. Importantly, the technique

allows researchers to create large numbers of genetically identical

IPS cells, because all cells in the mouse contain the same number of

viral integrations in the same location within the genome. With

previous approaches, each reprogrammed cell differed because the

viruses used to insert the reprogramming genes could integrate

anywhere in the cell's DNA with varying frequency.

Wernig and Lengner's method also increases the reprogramming

efficiency from one in a thousand cells to one in twenty.

The large numbers of IPS cells that can be created by this method can

aid experiments requiring millions of identical cells for

reprogramming, such as large-scale chemical library screening assays.

" In experiments, the technique will eliminate many of the

reprogramming process's unpredictable variables and simplify

enormously the research on the reprogramming mechanism and the

screening for virus replacements, " says Jaenisch, who is also a

professor of biology at Massachusetts Institute of Technology.