Stem Cell Exploration Thriving
at U-M

Sue O’Shea Photo: D.C. Goings

Doug Engel Photo: Martin Vloet

What a difference a year makes. It was just over 12 months ago when Sue O’Shea, Ph.D., learned that she would receive $2.3 million from the National Institutes of Health to establish an “Exploratory Center for Human Embryonic Stem Cell Research” — one of only three such centers in the country.

Today, the U-M Medical School’s embryonic stem cell laboratory is a frequent destination for U-M scientists, post-docs and graduate students who are studying one of three human embryonic stem cell lines available in the center. Two technicians and a lab manager handle the care and feeding of the notoriously finicky stem cell colonies, and also train researchers to work with the cells. Seven U-M scientists have received funding from the center to support pilot research studies with human embryonic stem cells. A new graduate course in stem cell biology is standing room only, and plans are underway to host an international symposium on stem cell science.

“We’ve had more requests for training by researchers and technicians than we can possibly respond to,” says O’Shea, a professor of cell and developmental biology. “The interest has been very gratifying, but literally overwhelming. It’s a good problem to have.”

Embryonic stem cells are primitive cells removed from a five-day-old embryo called a blastocyst. When grown in a culture dish under the right conditions, these cells retain the ability to self-renew, or make copies of themselves, indefinitely. Using growth factors, scientists are learning to make embryonic stem cells differentiate, or change, into any type of cell in the human body.

Funded by the National Institute of General Medical Sciences, the new research center was created to provide U-M scientists with a local source of human embryonic stem cells and access to the specialized equipment and training required to work with them.

“Nobody’s lab is set up for research with human embryonic stem cells, because they require a degree of care that most people don’t take when working with cell lines,” O’Shea says. “So for now, U-M investigators work with our technicians inside the core laboratory facility. Eventually, we hope to train people to do the work in their own labs.”

The original colonies of human embryonic stem cells in the U-M research center came from WiCell Research Institute in Madison, Wisconsin; BresaGen of Athens, Georgia; and the University of California, San Francisco. They are all federally approved sources of stem cell lines for use in NIH-funded research.

O’Shea spent the last year working with center technicians to develop quality control procedures to ensure that cell lines in the research center are free of chromosomal abnormalities and contaminants. Stem cell colonies are tested frequently to make sure they remain in the same pure undifferentiated state in which they were received. “Quality control is important, because the cells need to be identical. We don’t want to create a Michigan sub-clone of the Wisconsin cell line,” O’Shea says.

Doug Engel, Ph.D., the G. Carl Huber Professor of Developmental Biology and chair of the medical school’s Department of Cell and Developmental Biology, directs one of the current U-M studies using human ES cells from the new center. Engel is studying how hematopoietic, or blood-forming, cells grow early in an embryo’s development.

“The reason scientists want to pursue research with human embryonic stem cells, as well as with more specialized adult, or tissue, stem cells, is that we don’t know the true potential for either,” he says. “We need to continue both avenues of research until we find out that one is superior to the other. My guess is both types of stem cells will end up being important for different uses.”

O’Shea credits financial support from the Endowment for the Basic Sciences — a program created by Dean Allen S. Lichter, M.D. — with helping her get the new embryonic stem cell center up and running so quickly. In fact, without an initial pilot grant of $500,000 from the endowment, she doubts that her proposal for an NIH-funded center would have been approved at all.

“It was hugely important, because it allowed us to start up the core,” O’Shea says. “One of the factors NIH looks for is institutional commitment. The fact that we already had a lab in place and stem cells in hand made it possible for us to compete successfully with other universities that have made substantial investments in human ES cell biology.”

The endowment was established in 2002 with funding from the Dean’s Office. It is managed by chairs and directors from the medical school’s nine basic science departments and institutes, who decide together how to distribute proceeds from the endowment. They can be used for recruitment, retention, equipment purchases or to support new research initiatives, like O’Shea’s human embryonic stem cell laboratory.

“Creating the endowment was really a stroke of genius on the dean’s part, because it has forced us to think institutionally and invest in areas that will benefit research in multiple departments,” says Engel. “To my knowledge, no other medical school has a program like this that puts the decision of where science should be going in the hands of department chairs.”

—SFP