Cardiac predecessor cells appear to rejuvenate the hearts of older animals, according to a recent study from Cedars-Sinai Heart Institute that may lead to tests in humans.

Signs of rejuvenation in rats included a 20 percent increase in exercise capacity, faster regrowth of hair, and lengthening of the protective caps of chromosomes.

The study used cardiosphere-derived cells, or CDCs, which are like stem cells, but can only develop into heart cells. These cells are already being used in a human clinical trial to repair damage from heart attacks. The trial is being conducted by Beverly Hills-based Capricor in several hospitals, including Scripps La Jolla.

Since these cells have already been found to be safe, it should be fairly straightforward to extend testing from repairing heart damage in people to rejuvenation, said study leader Dr. Eduardo Marbn. Hes director of the Los Angeles Institute, part of Cedars-Sinai Medical Center. Marbn is also a co-founder of Capricor, publicly traded on Nasdaq.

However, a researcher not involved in the study said that while it was well done, the history of stem cell treatments indicates that proving efficacy in people promises to be far more difficult.

The study used cells taken from newborn rats, injected into the hearts of older, senescent rats. It was published Aug. 14 in the European Heart Journal.

The study is exceptional in both its scope and breadth, said Dr. Richard Schatz, a Scripps Clinic cardiologist involved in the Capricor trial at Scripps La Jolla.

It examines an extraordinary number of variables rarely seen in such studies to ask the question of the impact of CDC (specialized stem cells) on cardiac aging in rats, Schatz said by email. Every parameter of how aging might be studied moved in the right direction, meaning there might be a biologic effect of their cells throughout the body.

Schatz cautioned that scientific excellence doesnt equal clinical success.

The technologys muscle-improving effectiveness could also help patients with Duchenne muscular dystrophy, Marbn said. That use is in clinical testing by Capricor. Early results in patients have been promising enough that more studies are planned.

Capricor clinical trial information is available at http://capricor.com/clinical-trials.

Marbn said the study adds to growing evidence that progenitor cells exert their healing power by secreting chemicals that stimulate repair, not by permanently incorporating themselves into the body. The chemicals are enclosed in tiny vesicles called exosomes that the cells shed.

Until fairly recently, exosomes were dismissed as cellular debris, but are now being appreciated for their role in cell signaling, Marbn said.

There's a staggering number, something like 100 billion to a trillion exosomes per drop of blood, per drop of cerebrospinal fluid, Marbn said. They are plentiful in breast milk. The only thing we know right now is that there is a complex signaling system.

These exosomes travel far beyond the heart to reach skeletal muscle, which is weakened in Duchenne muscular dystrophy, he said.

Schatz said the study provides evidence that the cells exert many different effects beyond those in a single target organ, through the exosomes, seen in humans as well.

This is very good news if you are a rat, but the obvious limitation is how will this play out in humans, Schatz said.

Previous clinical trials of stem cells have been successful in Phase 1 and 2, Schatz said, but fail in Phase 3. So the researchers face a daunting road ahead to demonstrate usefulness in people.

This does not take away from the brilliant science behind this exceptional group of investigators, Schatz said. They should be congratulated for a very thoughtful and expansive look at a fascinating subject, the clinical relevance of which remains to be seen.

The rejuvenation effects to some degree resemble cells created when adult cells are reprogrammed back to being stem cells, Marbn said.

Certain factors are turned on that regress the cells to act like embryonic stem cells. These are called induced pluripotent stem cells, because they can become nearly any cell in the body, a property called pluripotency.

Something like this might be happening through exosome-mediated reprogramming.

We have a suspicion that even though we didn't go about trying to activate those factors, some of them may in fact be turned on by the therapy, Marbn said.

Understanding precisely what is going on will take much more work to sort out, he said. For example, lengthening the protective caps of chromosomes, or telomeres, is presumably caused by production of telomerase, an enzyme that makes them longer. But how?

Knowing the exosomes are involved doesnt narrow it down very much, he said.

We think that there's thousands and thousands of different bioactive molecules within exosomes. And so I can't right now point to, let's say, these five RNAs and say, they're the ones that we think are doing the trick, Marbn said. But somewhere in the genetic instructions in the exosomes are signals that cause telomerase to be activated and elongation of the telomeres.

Even without understanding the precise mechanism, the demonstrated results have been promising enough for Capricor to continue clinical testing in Duchenne muscular dystrophy, Marbn said, even though its outside the companys initial focus on heart disease.

The heart attack research gave mixed messages, he said. Capricor isnt abandoning it, but has given priority to the muscular dystrophy program.

Duchenne muscular dystrophy patients and their parents are more interested in increasing skeletal muscle function than heart function, he said. The disease virtually exclusively affects males, and they often die when quite young.

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Young cardiac cells rejuvenate hearts, in animal study - The San Diego Union-Tribune

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