S is for Stem Cells

The goal of every serious exercise program is to lose fat and replace it with muscle. But outside the research laboratory, few people realize that both fat and muscle - as well as bone and cartilage - all stem from, well, the same type of "mesenchymal" stem cell.

It is a remarkable reality that the School of Dentistry researcher Rik Derynck and his growth- and-development laboratory colleagues marvel at each day as they seek to discover the rules and tools that guide these cells down four different paths.

Of course, given the national debate over the use of stem cells in scientific research, some might assume that all such investigations are, by their very nature, controversial. Putting aside the benefits and risks now being weighed (see sidebar on UCSF's plans to create a program in stem cell biology) what such assumptions ignore is the existence of both embryonic and adult stem cells. Embryonic stem cells, as their name implies, transform the fertilized egg into an embryo that becomes a newborn, with all the organs, tissues and skeletal structure that we associate with healthy offspring. Their job done, embryonic stem cells disappear. The body's repair- and-replenishment tasks then become the responsibility of adult stem cells, which have a more limited assignment. They can only make one or a handful of tissues.

Such is the case with Derynck's mesenchymal cells and their four-way street of possibilities. "I'm a signaling scientist," says Derynck, who specializes in understanding the communication systems cells use to orchestrate their activities. "I want to know what kind of signaling is involved from the outside of the cell into the nucleus that makes mesenchymal cells differentiate." The goal is not to turn fat cells into muscle cells with a "signaling pill," although the Belgian researcher is quick to point out the evolutionary injustice that transforms cells destined to become bone cells into fat cells with age - and his lab's success in reversing that process in cell culture. What concerns him more are the more dramatic injustices that manifest themselves as human craniofacial defects. "We have learned in our experiments with mice that even slight perturbations in the bone cell signaling process can have an enormous impact on skeletal and especially, craniofacial development."

In fact, the Program in Craniofacial and Mesenchymal Biology was the brainchild of both Derynck and Dentistry's Growth and Development chair Karin Vargervik, who has directed UCSF's famed Center for Craniofacial Anomalies (see UCSF Magazine, September 2001) for decades. "I'm not a bone biologist," says Derynck," but what we are learning about different growth factors like transforming growth factor ß (TGF-ß) is that changes in the signaling cascade can change how successfully bone forms." They also can influence how bones come together to form a complicated structure, such as the human skull and face. This is to say nothing of the countless thousands who would benefit from new insights into and treatments for such diseases as osteoporosis and osteoarthritis. Says Derynck, "UCSF is perhaps the only place in the country right now where this kind of formal program exists. And I think when it comes to having a future impact at the bedside, we are really going places."

by Jeff Miller