Heart stem cells trial mostly disappoints but is oversold

Are there endogenous adult heart stem cells that are useful in cardiac disease or can stem cell infusions help ailing hearts?

As to the first question, the adult heart does not appear to have meaningful numbers of true stem cells. Further, testing the idea of infusions of stem cells for heart disease has so far been giving largely negative results over two-plus decades.

Clinical trial after trial just keeps producing discouraging news.

Even so, the results and ideas have often been viewed too positively or even hyped.

I recommend this recent review article by leaders in the field that gives a helpful chronology and highlights major challenges in the cardiac cell therapy arena. Their overview of cell therapy trial data is excellent.

Heart stem cells trial misses primary and secondary endpoints

With that context in mind, let’s take a look at a new stem cell infusion cardiac trial. The trial’s primary sponsor was Mesoblast. 

In this study, bone marrow mesenchymal precursor cells (MPCs) were directly infused into the heart. Why would that help? I’m not sure but it seems the idea is an anti-inflammatory kind of effect.

How’d the trial turn out?

In the big picture it failed to meet its primary and secondary endpoints. In a subgroup of patients with inflammation, a post-hoc analysis was encouraging for the cell therapy recipients. So overall this is a negative study with perhaps helpful data to guide future studies of MPCs and similar cells.

Media coverage is generally positive however

Yet somehow the trial has been portrayed in the media as generally a big step forward. Here is some of the coverage of the newly completed trial:

• We have USA Today “After years of failure, study finds hearts were ‘pumping stronger’ after stem cell therapy” from Karen Weintraub.
• CNN ran with “Stem cell therapy may reduce risk of heart attack and stroke in certain heart failure patients, study shows.”

While the CNN headline is phrased appropriately cautiously, the article mostly fails to capture the complexities and negative results here. In contrast, the USA Today headline is a misstep, but Weintraub does a good job of covering the trial’s actual data in the text of her piece.

Again, there are some signals of possible benefits with post-hoc analysis, especially in a subgroup with inflammation, but it’s unclear what that means. More clinical work would be necessary to figure it out. Do the data justify that? Perhaps?

Weintraub quotes cardiac cell therapy researcher Roberto Bolli of the University of Louisville:

This is first large study of stem cell therapy in heart disease to show an improvement for patients, Bolli said. “That’s very significant.”…”I would say cell therapy is a promising treatment for chronic heart failure,” Bolli said.

This seems somewhat too upbeat to me.

Notably, the actual press release on this trial doesn’t mention the primary and secondary endpoints. That’s a mistake.

Looking ahead

In my view, the cardiac cell therapy field has to be extra cautious in interpreting trial results. The Piero Anversa debacle with nearly three-dozen retractions makes this even more important. Also, cardiac cell therapy trial data so far have generally been discouraging. That may make it tempting to overstate results or focus on post-hoc analyses as people are looking for good news, but it should instead be another reason for caution in how things are portrayed to the public. I realize there are many complex driving factors here though in how things are portrayed.

I asked stem cell biologist and cardiac researcher Benoit Bruneau about the new publication and here was his reaction:

“The positive here is the apparent effect on inflammation, but without a positive clinical outcome I only see, as they state, hypothesis-generating signal to be explored further.”

Given the massive problem of heart disease including specifically heart failure, it makes sense to continue to pursue cell therapy further, but change is needed. I like the way the review article I cited earlier ends, “With a stronger commitment to a science-driven approach to the challenges of heart regenerative therapeutics, perhaps we can provide renewed hope for patients with advanced heart failure.”

I hope that findings are more encouraging in the future but it has to be data-driven.

Also, what are the new ideas here to move forward from past negative trial results? Is focusing on heart disease patients with inflammation the best way when using MPCs or MSCs?

Should there be a major focus on other cell types?

References

• Review of the cardiac cell therapy arena.
• The  new stem cell infusion cardiac trial. 
• Clinicaltrials.gov trial listing