Method For Generating Novel Types Of Stem Cells

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Method For Generating Novel Types Of Stem Cells

26 Dec 2008

http://www.medicalnewstoday.com/articles/133790.php

Breakthrough may offer opportunity for expanding research, drug

discovery

The study, which appears in the online version of Cell Stem Cell and

the January 2009 print edition of the journal, provides proof of

principle that alternative sources of stem cells can be created.

The team, which included scientists from Scripps Research, Peking

University, and the University of California, San Diego, conducted

the studies to establish novel rat induced pluripotent stem cell

lines (riPSCs) and human induced pluripotent stem cell lines (hiPSCs)

by using a specific cocktail of chemicals combined with genetic

reprogramming, a process whereby an adult cell is returned to its

early embryonic state. Pluripotency refers to the ability of a cell

to develop into each of the more than 200 cell types of the adult

body.

Mimicking Human Physiology

Scientists genetically engineer embryonic stem cells to create mouse

models that contain the engineered genes - so-called transgenic

animals - in the hope of applying the knowledge gained from studying

such mice to benefit humans. Although using mouse pluripotent

embryonic stem cells has been the standard since these cells were

first derived in 1981, researchers have long wanted to apply such

powerful techniques to other animal species to help the study of

human physiology and disease.

The major advantage of using other animal species, such as rats, is

that the physiology of these animals can better mimic human

physiology, for example, in studies of metabolic and neurological

diseases. The size of other animals also is an advantage because

larger organs and tissues are easier to work with. Because of these

benefits, scientists have created transgenic animals from species

other than mice, but the lack of pluripotent stem cells from these

species and the tedious and imprecise techniques currently available

has made the process difficult.

" Mouse models created with pluripotent embryonic stem cells are

wonderful tools for understanding the fundamental biology of genes, "

says Sheng Ding, Ph.D., an associate professor in the Scripps

Research Department of Chemistry who was senior author of the study

with Peking University investigator Hongkui Deng, Ph.D. " But in some

important ways these models are less than ideal. Our demonstrated

technologies will enable unprecedented and broad applications for

better creating animal models from other species. "

Novel and More Robust Human Pluripotent Stem Cells

In another closely related aspect of this work, Ding has also shown

that a new kind of human pluripotent stem cell can now be created

using the same chemical and reprogramming methods used to create the

rat pluripotent stem cells. Human pluripotent stem cells hold promise

for modeling human development and disease, testing drugs, and

providing unlimited functional cells for cell replacement therapy.

" Recent studies have found, however, that conventional human

embryonic stem cells represent a different pluripotent cell type and

are not the counterpart of the conventional, and most useful, mouse

embryonic stem cells, " Ding says.

The issue is that pluripotent stem cells can be represented by cells

from two distinct stages of embryonic development - the early pre-

implantation blastocyst stage and the later post-implantation

epiblast stage. Today, conventional mouse embryonic stem cells

represent the pre- implantation stage pluripotent cells, and human

embryonic stem cells appear to represent later post- implantation

stage pluripotent cells.

Early- and late-stage cells have very different properties. For

example, they respond differently to the same signals given to stem

cells to differentiate into specific types of cells. The pre-

implantation stage of cells will differentiate into one type of cell,

while post-implantation stage of cells will turn into other types of

cells. Their propensity toward specific cell types and growth

properties are also different. The novel human pluripotent cells

created by the scientists appear to represent the early stage of

pluripotent cells - closer to well researched conventional mouse

embryonic stem cells - and grow with better properties.

" The different behaviors of the pre- and post-implantation

pluripotent stem cells means that findings from research done on

mouse embryonic stem cells are often not translatable to work done on

human embryonic stem cells, " Ding says. " With our new human

pluripotent stem cells, we again have proof of principle that human

stem cells can be created that are similar to mouse embryonic stem

cells. The knowledge gained from mouse studies, therefore, will be

more directly translatable to human cells, offering an advantage in

biomedical research. "