The promise of stem cell therapy has excited cardiovascular scientists for years. In theory, tackling heart failure with stem cells makes sense. Weak or scarred heart muscle is a major cause of heart failure, so using regenerative stem cells to repair scar tissue appears to be a logical antidote to the problem.

But the latest trial of one such experimental stem cell therapy has left its manufacturer scrambling to salvage it.

In a 271-person heart failure study presented this week at the European Society of Cardiology Congress, there was no difference in deaths or worsening of heart failure between patients given Celyad’s C-Cure and those given a sham procedure.

The product did, however, benefit a subset of patients — those with severely enlarged hearts — so Belgium-based Celyad is refocusing its efforts on them. It plans to meet with European regulators to seek approval for the product for such patients. The company said it will also reach out to the Food and Drug Administration to discuss adjusting the protocols for its planned U.S. trial to reflect the more specific patient pool.

But Celyad needs $25 million to start the CHART-2 study of 400 U.S. patients, so it is seeking a partner to bankroll the research. Its quest comes at a time when the market is sending mixed signals about financing cardiac stem cell trials.

Last June, Teva Pharmaceuticals backed out of funding Australia-based Mesoblast’s stem cell therapy to treat heart failure. Last year, BioCardia scrapped its $50 million initial public offering due to weak demand, raising questions about how it would underwrite late-phase testing of its cardiac stem cell treatment. However, late last month, BioCardia announced it had agreed to merge with Tiger X Medical Inc., an agreement that would provide cash to support the trial.

“We have a study that says the treatment can work,” said Christian Homsy, M.D., Celyad’s chief executive. “There is a case to be made for investing in this kind of treatment.”

The problem facing Celyad and its brethren is a lack of positive results from large-scale clinical trials. Such evidence is crucial to convince investors like large pharmaceutical companies to commit the hundreds of millions of dollars necessary to foster products through development and regulatory approval.

“We are still at an immature stage in the field,” said Joshua Hare, M.D., founding director of the Interdisciplinary Stem Cell Institute at the Leonard M. Miller School of Medicine at the University of Miami, who was not involved in the C-Cure study. “We’ve probably only seen [cardiac stem cell] test results from 1,000 patients. We will never make heads or tails out of these treatments until we see them in 10,000 people.”

The first half of 2017 will bring highly anticipated data from Mesoblast and Capricor Therapeutics, which along with Celyad are among the most invested in the field. However, those trials also only studied a relatively small number of heart failure patients.

In the first quarter, Mesoblast will release interim results on about 300 patients from its ongoing phase 3 study of 600 people. Mesoblast chose to take an early look in the hopes that positive results will attract funding in the wake of Teva’s exit.

“We are [all] at an important time,” said Silviu Itescu, M.D., Mesoblast’s chief executive. “We are going to see if these therapies can really make a difference.”

Beverly Hills-based Capricor will analyze its six-month phase 2 study data of about 120 patients in the first half of next year. Janssen Biotech Inc. has 60 days to decide whether to exercise its right to license the treatment, known as CAP-1002. Capricor could receive up to $325 million plus royalties if a deal is reached.

Linda Marban, Ph.D., president and chief executive officer of Capricor, said Janssen has the financial strength to conduct the large trials the FDA needs to consider the product for approval. To date, the few treatments involving stem cells that have been FDA-approved are for blood and immune system diseases.

“What the small companies need to do is show proof of concept. You have to hit your endpoints,” said Marban.

There is a desperate need for new therapies to treat heart failure, a chronic condition that prevents the heart from pumping blood as it should. The number of American adults with the disease could top 8 million by 2030, up from 5.7 million in 2012, while the cost of treatment could more than double, from $31 billion to $70 billion.

Each firm is taking a different approach to reach the same goal: bolstering the deteriorated muscle.

Celyad uses a patient’s own cells for treatment, eliminating the risk of rejection. It draws a patient’s bone marrow stem cells, treats them with growth factors that coax them to become cardiac progenitor cells and then injects them into the heart via a special catheter.

Both Mesoblast and Capricor use donor cells to make their treatments. Executives at each company say it is more cost-effective and commercially viable to develop products for broad swaths of patients.

“We can qualify our cells with certain markers and release criteria so you know they are the same, time after time after time,” said Capricor’s Marban.

Capricor’s product uses heart-derived cells, which the company believes are especially qualified to treat cardiac disease. It administers the treatment through a coronary artery — a method it believes is a more effective delivery system.

Meanwhile, Mesoblast’s calling card for its therapy is a dose of 150 million mesenchymal precursor cells that are injected into the damaged heart muscle.

“Their methods are unique,” Hare said, “but it is too soon to say if one is better than the other. We just need to do more research. Without that we are left with a quandary in the field.”