Halfway through its initial ten-year mandate, the California Institute for Regenerative Medicine (CIRM) in San Francisco is confronting a topic familiar to anyone at middle age: its own mortality.

The publicly funded institute, one of the world’s largest supporters of stem-cell research, was born from a state referendum in 2004. Endorsements from celebrities such as then-state governor Arnold Schwarzenegger and the late actor Christopher Reeve, who had been paralysed by a spinal injury, helped to garner voter support for a public bond to underwrite the institute. But with half of the US$3 billion that it received from the state now spent and the rest expected to run out by 2021, CIRM is now actively planning for a future that may not include any further state support.

“It would be premature to even consider another bond measure at this time,” wrote Jonathan Thomas, CIRM’s chairman, in a draft of a transition plan requested by the state legislature. Thomas outlined the plan on 24 January at a public hearing held in San Francisco by the US Institute of Medicine, which CIRM has asked to review its operations.

Given that California is facing severe budget shortfalls, several billion dollars more for stem-cell science may strike residents as a luxury that they can ill afford. It may also prove difficult for CIRM’s supporters to point to any treatments that have emerged from the state’s investment. So far, the agency has funded only one clinical trial using embryonic stem cells, and that was halted by its sponsor, Geron of Menlo Park, California, last November.

Yet the institute has spent just over $1 billion on new buildings and labs, basic research, training and translational research, often for projects that scientists say are crucial and would be difficult to get funded any other way. So the prospect of a future without CIRM is provoking unease. “It would be a very different landscape if CIRM were not around,” says Howard Chang, a dermatologist and genome scientist at Stanford University in California.

“It would be a very different landscape if CIRM were not around.”

Chang has a CIRM grant to examine epigenetics in human embryonic stem cells, and is part of another CIRM-funded team that is preparing a developmental regulatory protein for use as a regenerative therapy. Both projects would be difficult to continue without the agency, he says. Federal funding for research using human embryonic stem cells remains controversial, and could dry up altogether after the next presidential election (see Nature 481, 421–423; 2012). And neither of Chang’s other funders — the US National Institutes of Health (NIH) and the Howard Hughes Medical Institute in Chevy Chase, Maryland — supports his interdisciplinary translational work. Irina Conboy, a stem-cell engineer at the University of California, Berkeley, who draws half of her lab’s funding from CIRM, agrees that in supporting work that has specific clinical goals, the agency occupies a niche that will not easily be filled by basic-research funders. “The NIH might say that the work does not have a strong theoretical component, so you’re not learning anything new,” she says.

CIRM is developing plans to help its grantees to continue their work if the agency closes. One option is a non-profit ‘venture philanthropy’ fund that would raise money from private sources to support stem-cell research. The agency is also writing a strat­egic plan for the rest of its ten-year mandate that focuses on translating research into the clinic, acknowledging that CIRM’s best shot at survival — and at sustaining future funding for stem-cell researchers — could come from a clinical success.

As CIRM board member Claire Pomeroy, chief executive of the University of California, Davis, Health System in Sacramento, noted at the agency’s board meeting on 17 January: “If you asked the public what they would define as success, they would say a patient benefited.”