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?

heart stem cells
“Dr. Emerson Perin holds up adult stem cells.” Texas Heart Institute.

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:

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?


6 thoughts on “Heart stem cells trial mostly disappoints but is oversold”

  1. I’ve been researching mesenchymal stem cells (MSCs) on the internet for years now. I first originally learned about MSCs when Joe Rogan interviewed Mel Gibson back in 2018, You’ve seen this interview before right Paul?


    Paul all I can tell you is keep your eyes on umbilical cord derived mesenchymal stem cells, or placenta derived mesenchymal stem cells for that matter. I truly believe that if Mesoblast had decided to use umbilical cord or placenta derived MSCs they would have had much better results.

    You remember that clinical trial by UC Davis health for spina bifida using placenta MSCs right?

    MSCs taken from the umbilical cord or the placenta are ultra young, these are super young stem cells and they are superior to bone marrow MSCs, because they’re younger, that’s as young as you can get basically when you collect MSCs from the placenta/umbilical cord.

    Right now there are multiple clinical trials in the USA using umbilical cord MSCs so I guess we’ll find out what happens.

    Also keep an eye on exosomes. Mesenchymal stem cell derived exosomes are extremely exciting. And there are multiple clinical trials in the USA using exosomes as well.

    Paul what’s your opinion on exosomes?

  2. As an addenum: another p. All in all there weren’t that many deaths in either group; it might be more followup (or a better established surrogate marker) would have been needed to show improvement…

  3. Adult heart harbors stem cells. You may wish to refer to our paper on studies done on mouse heart.DOI: 10.1007/s12015-021-10119-9

  4. Wha a load of Trollope you written you actually hate Mesoblast and I know the reason .I will be keeping your comments and will headline them all over place when success is achieved

  5. Its certainly less brilliant than its portrayed as. Being generous, looking at the HR the all-cause mortality and admissions dont seem too far away from significance… I’m guessing if it turned out (in some future trial) there *was* an improvement in those that would be in keeping with the otherwise paradoxical lower incidences of stroke/infarct and improved EF.

    Another good question besides type of cell is whether this is the best way to use mscs in this context; AFAIK their effect is usually paracrine rather than them differenciating directly onto anything. So maybe a relatively small injection of transendocardial MSCs (plus the damage of said injection) is not ideal, and there would be more mileage out of systemic administration of greater doses, or even MSC secreted factors, without the cells themselves?

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