California’s $3 billion stem cell agency, which is nearing the end of its financial life, announced Tuesday it is losing its president as the agency enters what some describe as the “last stage” of its 12-year operation.

The departure of C. Randal Mills, who joined the agency three years ago, came as an unwelcome surprise to followers of the California Institute for Regenerative Medicine, known as CIRM. Mills will leave at the end of June to become president of the National Marrow Donor Program in Minneapolis, the world’s largest bone marrow donor program.

Maria Millan, vice president of therapeutics at the agency, will become its interim president in July. The agency’s governing board plans a meeting of its search committee that month to consider options for a permanent replacement.

The agency expects to run out of cash for new awards in three years. Just last week, the prestigious journal Nature described the Oakland-based agency as entering its “final test” and “last stage.”

CIRM was created by a ballot initiative and bond issue in 2004 after a $34 million campaign that made the case that stem cell therapies were just around the corner. The agency has yet to finance a widely available therapy.

Mills, 45, joined the agency almost exactly three years ago and launched a more focused effort than any before to fulfill the promises and expectations created by that 2004 ballot initiative campaign.

In an interview, Mills said the offer to lead the donor program “came out of the blue.” The organization, he said, “does not do anything that doesn’t save lives.”

Mills said Millan was the obvious choice to succeed him on a permanent basis. Millan is a physician who has been with the agency since 2012, joining from StemCells Inc., where she was acting medical officer and vice president. Prior to that, she was an associate professor of transplant surgery for eight years at Stanford University.

Jonathan Thomas, the agency’s chairman who recruited Mills, said in a news release: “CIRM has experienced a remarkable transformation since Randy’s arrival. He has taken the agency to a new level by developing and implementing a bold strategic plan, the results of which include an 82 percent reduction in approval time, a three-fold increase in the number of clinical trials, and a 65 percent reduction in the time it takes to enroll those trials.”

Asked for comment, UC Davis stem cell researcher Paul Knoepfler said in an email: “Overall CIRM has prospered under Mills’ leadership with important, concrete accomplishments during his tenure. The agency’s current trajectory is also very positive.

“The timing of his departure probably isn’t ideal as CIRM looks to the future with some challenges such as the nature of future funding for the agency.”

John M. Simpson of Consumer Watchdog, a longtime observer of the agency, said in an email: “Dr. Mills made substantial contributions to the agency during his tenure, improving both efficiency of the grant-making process and transparency of CIRM’s operations. Given the uncertain future as CIRM’s current funding winds down, it is not at all surprising that he has opted to move on to another opportunity.”

Mills’ departure comes as supporters of the agency worry whether its work will effectively end in June 2020. Its first chairman, Bob Klein, is talking about asking California voters for another $5 billion. Klein also led the 2004 campaign.

Klein’s organization, Americans for Cures, is planning to conduct a poll this fall to determine the level of public support for CIRM. He has said that if support is in the 70 percent range he would mount a bond issue in 2018. Otherwise, he might try in 2020, a presidential election year, with a larger voter turnout.