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. Induced pluripotent stem cells (iPSCs) changed our field so dramatically that their discovery led to Shinya Yamanaka’s Nobel Prize just four years later.

New cell lines

Although 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 were not 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 to bring a concept proposal to our Board for the New Cell Line awards, including the option of developing human iPSCs. While Yamanaka had first reprogrammed mouse skin cells to iPSCs 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 simultaneously publish the creation of human iPSCs which CIRM staff annotated in the New Cell Line Request for Applications before posting 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 iPSCs work.”

Other iPSCs projects

• 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 iPSCs from people with diseases, also to develop better models of disease;
• ways to make iPSCs 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 iPSCs matters in the resulting stem cell;
• comparing iPSCs and ESC lines to see if they are truly equivalent.

Those turned out to be critical questions for the field, and many still dominate much of the research today.  One of the most robust areas of iPSCs 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 New Cell Line grantee, Fred Gage at the Salk Institute in San Diego, was among the first to report physiological differences between nerves grown from healthy individuals and 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 iPSCs,” 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 iPSC-derived nerves to look for treatments for schizophrenia and bipolar disorder. Clearly, the CIRM team was onto something back in 2007.