UCSF, Karolinska Institute Scientists Explore Stem Cell Collaborations

By Jennifer O'Brien UCSF and Karolinska Institute scientists are exploring a possible exchange of each other's human embryonic stem cell lines, with the goal of carrying out complementary studies that would characterize the physical distinctions between what are considered some of the best stem cell lines in the field. The need for such analysis is great, says Arnold Kriegstein, MD, PhD, director of the UCSF Institute for Regeneration Medicine. In the early years of human embryonic stem cell research - some six years ago - scientists expected that all embryonic stem cell "lines," or batches, would have the same genetic and molecular characteristics. However, in recent years, they've discovered that each cell line has different properties that influence the ability of the cells to specialize, or differentiate, into specific cell types, such as brain, heart and liver cells. Since a key goal of stem cell research is to create specialized cells that could be transplanted into patients to treat damaged tissue, identifying the best cell lines to carry out these specialization efforts is critical. Scientists want to determine, for instance, which cell lines would be best suited for differentiating into dopamine-producing nerve cells to treat Parkinson's disease, or into cardiac muscle cells to treat heart disease, or into insulin-producing pancreatic cells to treat diabetes. "The question is, How do you select the lines you are going to use?" says Kriegstein. "Your decision may make a big difference. One line might be much better; another might not work at all. The decisions are already being made by research groups, and there is very little data to go on to guide those decisions. The potential collaboration is very exciting." Susan Fisher, PhD, UCSF professor of cell and tissue biology, would lead a UCSF effort examining which proteins are expressed by individual cell lines, while scientists at the Karolinska Institute would examine the genes that are turned on, or "expressed," in these lines. The timing of the proposed collaboration is particularly relevant for UCSF scientists, says Kriegstein, as the California Institute for Regenerative Medicine plans to issue its first round of funding for research grants on human embryonic stem cells in March. This state funding will allow California scientists to study cell lines that are not on the federal stem cell registry established by President Bush in August 2001. "We want to work with the best cell lines there are," says Kriegstein, "and the collaborative projects we hope to begin with the Karolinska Institute are needed urgently." There are 21 cell lines listed in the National Institutes of Health (NIH) registry, and some are being used more than others, says Kriegstein. And while there are 100 to 200 human embryonic stem cell lines worldwide, only a handful of this broader group has proven to be of high quality. UCSF derived two embryonic stem cell lines in 2001, and these, along with those from University of Wisconsin, are the only lines from US universities that qualified for inclusion in the NIH registry. Since then, scientists at UCSF have gone on to derive 11 new lines. Under current federal policy, these lines cannot be studied with federal funds. As for why there is genetic and molecular diversity in the cell lines, says Fisher, there are several likely factors. For one, contrary to previous thinking, morphologic evidence now suggests that the inner cell mass of the human blastocyst - from which embryonic stem cells are derived - is not made up of one homogeneous cell type. Rather, it contains clusters of cells that look quite different from one another. "As current procedures for deriving stem cell lines are essentially random, the cell type that grows best under the conditions that are employed emerges as the embryonic stem cell line," she explains. As a result, cell lines might begin by the proliferation of different cell types. "Their different behaviors subsequently could reflect their diverse origins." Other likely factors, she says, are the culture environment in which the cells are derived and nourished and the techniques by which the cells are derived. "Scientists at UCSF and the Karolinksa Institute will be exploring these factors, as well as characterizing the lines," says Kriegstein. The discussion of a potential collaboration came against the backdrop of a two-day stem cell symposium (Jan. 17-18) hosted by UCSF on the occasion of a visit to the University by scientists from the Karolinska Institute in Sweden. The Karolinksa Institute is a leading biomedical sciences institute in Europe and the institute that awards the Nobel Prize in Physiology or Medicine each year. The panelists, including seven stem cell scientists from each institution, presented findings related to embryonic, neural and mesenchymal stem cells, with an eye toward ultimately treating such illnesses as heart disease, Parkinsons's disease, and diseases of connective tissue and bone. "These were extremely valuable presentations," says Kriegstein. "While most talks began with information that was familiar, in each case they concluded with new material." A possible collaboration on neural stem cell research related to treating Parkinson's disease is also being considered, he says. "This promises to be the start of a valuable partnership between two great institutions." Related links: Karolinska Comes Calling: A Conversation with Harriet Wallberg-Henriksson, President of Sweden's Karolinska Institute UCSF Science Café, January 26, 2007 UCSF Institute for Regeneration Medicine