Connecticut's continuing role in advancing stem cell research.

New Haven was the proud host of StemCONN 09, Connecticut’s International Stem Cell Research Symposium, in March. Buzzing with academic researchers, students, and biotech entrepreneurs, it was the second such conference in the state since Connecticut became the third state to devote funds to stem cell research. The symposium highlighted work that otherwise would have required private money. Under President George W. Bush, policy limited federal funding to research on human embryonic stem cell (hESC) lines derived prior to 9 p.m. on August 9, 2001. That federal ban on funding the creation of and work with new hESC lines, given that the available lines were far fewer than initially expected and lacking in genetic diversity, first galvanized New Jersey and California to open up their own coffers to researchers in 2004. In June 2005, Connecticut Gov. M. Jodi Rell followed suit, signing legislation allocating $100 million over 10 years for stem cell research. Warren Wollschlager, chief of the Office of Research and Development in the Connecticut Department of Public Health, recalled that despite the excitement, it wasn’t a great day for the department. The legislation mandated a stem cell peer review panel — but no money was provided for administrative support. Nevertheless, after poring through 70 applications, the state was ready to distribute its first awards by November 2006. Twenty-one grants from three institutions — the University of Connecticut, Wesleyan University, and Yale University — received funding, totaling just under $20 million. At the time, it was the largest award of public funding in any state. The public support for hESC research in Connecticut encouraged private sources to contribute as well. According to Diane Krause, M.D., Ph.D., because the state provided $10 million, Yale was willing to throw in an additional $80 million to create its stem cell center. At StemCONN, Krause was adamant that “Yale would not have a stem cell center without the Initiative” and went on to highlight Matthew Rodeheffer’s work on brown fat; Michael Snyder’s exploration of differential gene expression in neuronal differentiation; and Gene Redmond’s study of stem cells to treat Parkinson’s disease in primates, among others. Yale has 19 researchers with ongoing grants from the state. The university created hESC culture, genomics and bioinformatics, cell imaging, and FACS cores — all of which Krause says are “highly functional and very busy” — and was able to hire nine new investigators, including the director of the Yale Stem Cell Center, Haifan Lin. Recruited from Duke University, Lin focuses on PIWI/Argonaute genes, a particularly interesting group because they are the only known gene families required for stem cell self-renewal in both animal and plant kingdoms. Marc Lalande, Ph.D., of the University of Connecticut Health Center, told a similar tale of infrastructure development and recruitment. In 2006, the state awarded a $2.5 million grant to establish a joint UConn-Wesleyan University core laboratory. Ren-He Xu left the WiCell Research Institute at the University of Wisconsin to direct the core, which, as of February, had trained more than 100 scientists and by summer of 2010 will be relocated to a new $52 million, 117,000-square-foot research building on the Farmington campus. In 2008, the Xu lab announced the creation of two hESC lines, aptly named CT1 and CT2, which are available to outside researchers upon request. In addition to supporting stem cores and establishing cell lines, state funding also has enabled certain stem cell research projects with particular clinical applications. Laura Grabel, Ph.D., of Wesleyan University, explained that she began with a single grad student; now about 10 people are working on her research. Grabel’s work, in collaboration with Janice Naegele of Wesleyan and Gloster Aaron of the UConn Health Center, is to devise stem cell-based therapies for temporal lobe epilepsy (TLE). In TLE, recurring seizures often result in selective death of neurons in the hippocampus. If researchers can differentiate embryonic stem cells into neural stem cells, and ultimately create new neurons — including inhibitory neurons to limit brain excitability — they can begin to “fill in gaps” for the patients and ameliorate the disease. So far, Grabel’s data is promising; she can point to striking images of bright red neural rosettes, well on their way to becoming neurons, after just two weeks in culture. Indeed, the allure of stem cell research, particularly to the public at large, is the promise that multipotent cells will deliver in the clinic. Milton Wallack, co-chairman of the Connecticut Stem Cell Coalition, says that the goal ultimately is to “unlock the secrets of stem cells and move this research closer to therapies.” According to Wallack, Connecticut aims to continue its support of basic research, as well as targeting cancer, and begin to make regenerative medicine breakthroughs in 10 to 15 years. As of May 2009, five other states have followed Connecticut in their public support of stem cell research: New York, Maryland, Iowa, Massachusetts, and Illinois. Most dramatically, on March 9, President Obama signed an executive order rescinding President Bush’s 2001 limitations on hESC research [1]. At StemCONN, which took place just two weeks after Obama’s announcement, researchers were buoyed by the repeal, and Wollschlager was optimistic it “will bring the change so many scientists have fought for.” Although the Dickey-Wicker amendment is still in effect, it restricts funding only from hES line creation, so work with the new CT lines, for example, will likely be eligible for federal funds. The executive order itself did not detail which cell lines could or could not be used or in what ways, but instead deferred to the National Institutes of Health (NIH) to develop ethical guidelines within 120 days. The draft guidelines were made available in April to allow the public to comment on them; the final guidelines were established on July 7. One of many researchers who gave input to the NIH, Krause was disappointed that the “resulting guidelines still leave in place significant limitations to federal funding and have, temporarily, left the research community ‘on hold’ regarding federal funding while additional details are being worked out.” One of the primary drawbacks, says Krause, is that funding is provided only to hESC lines created using unwanted embryos following fertility treatment. This effectively excludes methods such as somatic cell nuclear transfer, which holds “particular promise for studying the genetic basis of certain human diseases.” Also troublesome is that because of the new guidelines’ more specific informed consent requirements, certain hESC cell lines previously funded under Bush may in fact no longer be eligible. As time passes, however, the collective changes to federal law will result in more, not less, eligible cell lines. With new opportunities for federal funds, coupled with the economic downturn that has wreaked havoc on many state budgets, it remains to be seen whether states with ongoing hESC research programs will continue to support them. But given that there is “still very limited” federal funding, and Connecticut law is clear about which lines can be studied, Krause is convinced state money is as important as ever. Wollschlager said that the 2007 conference celebrated the fact that Connecticut was “in the game;” the 2009 conference was able to celebrate the “work being done.” Researchers certainly hope the latter will be said of the next conference. For now, it appears they will be able to, since the recipients of the most recent grants, totaling $9.8 million, were announced in April.