ASCB Task Force Spots Three Opportunities for the Next Stem Cell Revolution

A task force organized by the ASCB to consider the next scientific steps in the stem cell revolution unveiled its preliminary report on Friday, November 15, 2013. The report highlighted three opportunities for using cultured human embryonic and human induced pluripotent (iPS) stem cells in both human and animal model systems. The ASCB Stem Cell Task Force predicted that the greatest scientific payoff for stem cell research in the next few years would come from strengthening our basic knowledge of cell and developmental biology, from better understanding genetic variation within and between species, and finally from taking advantage of what’s already been learned from stem cell biology about biological mechanisms to construct artificial or enhanced organs. The report, after being presented to a gathering of scientists in a downtown Bethesda, MD, hotel, was immediately posted for comment on the ASCB website.

Stem cell biology has been both exhilarating and humbling, Elaine Fuchs of the Rockefeller University and an ASCB task force member told an audience of researchers, science funders, and representatives from the National Institutes of Health and the Department of Defense’s Defense Advanced Research Projects Agency. Reviewing major milestones in tissue research since iPS cells revolutionized the field in 2007, Fuchs pointed out how much we have learned about how cells and tissues operate as systems but also how much we don’t know yet about extremely basic cell and developmental biology. The best stem cell work, Fuchs said, has all been “tiny” steps. “In order to get to these basic steps, it’s taken years of going back to basic biology,” she said.

Arshad Desai of the University of California, San Diego, is an experimental cell biologist probing the centriole, a fundamental organelle involved in everything from development to cancer. Desai told the group how stem cell biology offered his field tantalizing approaches toward a “new biology” that would give researchers better and more reliable model systems. But in the lab today, Desai said that stem cells are raising critical questions about basic concepts such as “wild type” or what constitutes valid reproducibility of an experiment. “Which line is ‘wild type’? Do we address different outcomes in different lines?” Desai asked. “Is it going to tell us what all these types of cells are doing under different conditions?” But Desai emphasized the potential of stem cells as transformative tools in cell biology, saying “There’s a lot of biology in this machinery.”

Lawrence Goldstein of the University of California, San Diego, and the chair of the ASCB task force, said that in working with iPS cells, he has come back time and again to fundamental issues of human genetics such as copy number variation within a single human being. Yet in his lab’s work on Alzheimer’s disease (AD), Goldstein sees research that only human-derived iPS cells can hope to tackle, such as sampling the genomes of individuals with the rare form of familial AD against those with sporadic AD. “Unfortunately, mice don’t develop AD,” said Goldstein. “There are many resemblances between mouse and humans but there is no good AD mouse model.” Because they are derived from patients, an iPS cell culture can sample and thus reflect a specific human genome, Goldstein said.

The ASCB Stem Cell Task Force grew out of a high-level ASCB strategic retreat in the spring of 2012 to identify key areas of cell science ripe for expansion.

Besides Fuchs, Desai, and Goldstein, task force members included ASCB President Don Cleveland of the University of California, San Diego, along with George Daley of Harvard Medical School; Rudolf Jaenisch of the Whitehead Institute at the Massachusetts Institute of Technology; Tony Hyman of the Max Planck Institute in Dresden, Germany; Ruth Lehmann of New York University School of Medicine; Fred Gage of the Salk Institute in La Jolla, CA; David Burgess of Boston College; Phil Newmark of the University of Illinois, Urbana-Champaign; Sally Temple of the Neural Stem Cell Institute; James Spudich of Stanford University School of Medicine; David Drubin of the University of California, Berkeley; and ASCB Past President Ron Vale of the University of California, San Francisco.

Also on the task force was ASCB Executive Director Stefano Bertuzzi, who told the group that political controversy surrounding early stem cell work had kept many researchers caught “like deer in the headlights” for too long. It was time to move on, said Bertuzzi, and use the tremendous potential of stem cell biology both to increase our knowledge of basic cell and developmental science and to bring that knowledge to bear on critical human health problems such as neurodegenerative disease and diabetes.

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