A microscope image showing a colony of induced pluripotent stem cells created by the U-M Consortium for Stem Cell Therapies. Photo: Sue O’Shea.
of Michigan’s Consortium
for Stem Cell Therapies has achieved another of its primary goals:
reprogramming adult skin cells so they behave like embryonic stem cells.
The reprogrammed cells are called induced pluripotent stem
cells, or iPS cells. They display many of the most scientifically valuable
properties of embryonic stem cells while enabling researchers to bypass embryos
U-M researchers will use the iPS cells side by side with
human embryonic stem cells to study the origin and progression of various
diseases and to search for new treatments. Three of the consortium’s first five
iPS cell lines came from skin cells donated by patients with bipolar disorder
and will be used to study that condition.
“The two main goals we had when we started the
consortium were to make human embryonic stem cell lines and iPS cell lines. Now
we’ve accomplished both those objectives,” says consortium codirector Sue
O’Shea, a professor of cell and developmental biology at the Medical School.
The Consortium for Stem Cell Therapies was formed in March
2009. In October 2010, consortium researchers announced they had created the
state’s first human embryonic stem cell line. Six months later they announced
they had created the state’s first human embryonic stem cell lines that carry
the genes responsible for inherited disease.
One of the consortium’s central goals has been to create
disease-affected cell lines of both iPS cells and human embryonic stem cells,
then to compare them.
“It’s a niche that we need to fill,” O’Shea says.
“We’re really poised to do something important by studying gene expression
and disease progression in both types of cells.”
When human iPS cells burst onto the scene in 2007, they were
heralded by some as likely replacements for the more controversial human
embryonic stem cells they mimic. But recent studies have uncovered some
important differences between iPS cells and human embryonic stem cells, and
most stem cell researchers say continued work on both types of cells—along with
adult stem cells—is needed.
“This is another major step forward for medical science
Now that we have proven that we can create both embryonic stem cell lines and
iPS lines carrying the genetic defects for specific diseases, we can really
begin exploring the causes and progression of those diseases, with the ultimate
goal of finding new therapies for patients,” says Dr. Eva Feldman,
director of the A. Alfred Taubman Medical Research Institute.
“We believe the day may not be too far off when we can
use stem cells to preserve and regenerate tissue damaged by disease. This truly
puts this university, as well as this state, at the forefront of medical
Consortium workers created the iPS cells using the most
common of several laboratory techniques: They used a virus to deliver four
genes that genetically reprogrammed human skin cells into an embryonic-like
state. Then, various tests were performed over a period of several months to
confirm that the reprogrammed cells are pluripotent, meaning that they have the
ability to produce all the cell types in the adult body. The skin cells were
donated by research volunteers.
“The production of iPS cells marks an important
milestone in the consortium’s progress toward understanding stem cell biology
and using this knowledge to treat devastating genetic diseases,” says Gary
Smith, professor of obstetrics and gynecology and co-director of the Consortium
for Stem Cell Therapies.
“Our next steps are to compare and contrast human
embryonic stem cells and iPS cells to identify their individual strengths and
limitations That will guide us toward evidence-based medical decisions as to
which type of stem cell should be used to understand disease onset and
progression, for drug-treatment screening, and for future cell replacement
The project required approval by U-M’s Human Pluripotent
Stem Cell Research Oversight Committee. The committee is composed of
physicians, scientists, ethicists, attorneys, and community leaders who
evaluated whether the project would be conducted ethically, legally, and to the
benefit of patients.
While the achievement is a first for the consortium, the
five new cell lines are not the first iPS cell lines created on the University of Michigan campus. U-M neurologist Jack
Parent’s laboratory created iPS cell lines more than a year ago for a study of
an inherited form of epilepsy called Dravet syndrome.
The consortium’s iPS cell lines will be shared with
researchers across campus, and consortium personnel will train other U-M
researchers in the techniques required to make iPS cells.
“This lab has the facilities and the expertise to
really help other people make the lines from patients carrying genetic disease
to facilitate studies of disease development,” O’Shea says.
Filed Under: Drug Discovery