Part of The Stem Cellar series on ten years of iPS cells
The first press release I issued that announced new research grants after arriving at CIRM in 2008 detailed 18 “New Cell Line” awards. Ten of those grants, announced in June that year, were for a type of stem cell that had not even been proven to exist until November the year before. Those induced pluripotent stem cells (iPS cells) so dramatically changed our field that their discovery led to the Nobel prize for Shinya Yamanaka just four years later.
Even though California voters approved the creation of CIRM in November 2004 and the agency’s first office opened just a few months later, the first grants for research projects did not get approved until February 2007. Litigation by opponents of stem cell research and the monumental task of setting up a granting agency from scratch resulted in a two-year gap between the vote and getting down to the business the voters resoundingly supported.
Those first research grants sought to increase the sparse number of California researchers actually doing research with human embryonic stem cells. But just eight months later, in October 2007, CIRM staff had enough confidence in the mettle of California’s researchers that they went to our Board with a concept proposal for the New Cell Line awards that included the option of developing human iPS cells. While Yamanaka had first reprogrammed mouse skin cells to iPS cells in 2006, at the time of the Board presentation it was only speculated to be possible with human tissue. Not until the following month did he and Wisconsin’s James Thomson simultaneous publish the creation of human iPS cells, which CIRM staff annotated into the New Cell Line Request for Applications before they posted it in December 2007.
Former colleague Uta Grieshammer managed the New Cell Line awards as a CIRM senior science officer. In a recent interview she said the scientific questions posed by those grants showed the value of these awards.
“The types of research we ended up funding under this call reflected the breadth of the questions important to embryonic stem cell and iPS cell work.”
Those projects included:
- Creating early stage embryonic stem cells (ESCs), called ICM stage, which had been done in mice but not humans;
- creating “clinical grade” ESCs fit for use in patients;
- creating ESCs from embryos discarded by families at IVF clinics because they carried mutations for inherited diseases with the goal of developing better models for those diseases;
- creating iPS cells from people with diseases, also to develop better models of disease;
- ways to make iPS cells that did not result in the reprogramming factors being integrated into the cell’s genes permanently, which could render them unfit for human therapy;
- looking to see if the age of the adult cell used to make iPS cells matters in the resulting stem cell;
- comparing iPS and ESC lines to see if they are truly equivalent.
Those all turned out to be critical questions for the field, many still dominating much of the research today. One of the most robust areas of iPS research involves creating disease-in-a-dish models using patient-derived stem cells for diseases that have been historically difficult to model in animals. One of the New Cell Line grantees, Fred Gage at the Salk Institute in San Diego, became one of the first researchers anywhere to report physiological differences between nerves grown from normal individuals versus nerves grown from patients with mental health conditions.
“The excitement to me personally with the result of our New Cell Lines is access to understanding complex genetic diseases through iPS cells,” said Uta, who currently is helping us untangle even more complex diseases as part of the management team for California’s personalized medicine initiative.
Gage, along with a co-investigator at Johns Hopkins, just last week received a $15 million grant from the National Institutes of Health to screen drug libraries against iPS cell-derived nerves to look for treatments for schizophrenia and bi-polar disorder. Clearly the CIRM team was onto something back in 2007.
Footnote: This will be my last regular post for The Stem Cellar. I will be retiring from CIRM later this month, though I may heed the call if my colleagues ask me to do a guest post from my new base on Cape Cod.