AHA – Distant promise of stem cells draws nearer

Analysis

For all the promise that has been mooted over the possible use of stem cells to repair hearts damaged by myocardial infarction or heart failure, the field has shown precious little success. Trial results disclosed at the American Heart Association scientific meetings still indicate slow progress, with mixed success from very early-stage work.

While researchers have shown they can safely infuse undifferentiated cells into injured heart tissues, evidence of efficacy has been elusive. Questions regarding the type of stem cells and timing of infusion also remain to be settled. However, much hope is still being placed in this treatment strategy. “One thing we’ve learned is that the heart does regenerate,” Dr Richard Becker, a professor at Duke University Medical Centre in North Carolina, told EP Vantage. “Now that we understand that, we must find out how it goes about doing that. Stem cells are a good place to start.”

Refinements

Much of the research detailed at the AHA meeting focused on identifying best practices in cardiovascular regeneration, with tests of both allogeneic and autologous tissue, as well as cardiac and bone-marrow-defined stem cells. Some of the most promising work has emerged from the phase I Scipio trial in ischaemic cardiomyopathy at the University of Louisville, which infused cardiac stem cells taken from tissues removed as part of a coronary artery bypass graft.

While this is a small study of 20 treated patients and 13 controls, begun in 2009, it now has two-year follow-up data indicating continuing significant improvement in left ventricle ejection fraction of treated patients through 24 months when compared with controls. The treated patients also see signs of tissue repair and significant improvements in heart failure score.

The trial’s chief investigator, Roberto Bolli, director of the university’s Institute of Molecular Cardiology, told EP Vantage at the AHA 2011 meeting that he was hoping to secure funding for a phase II trial of the technique (AHA 2011 – Positive data put stem cells in spotlight, November 17, 2011).

“I think this is among the most positive studies that I’ve seen, and begs a phase II trial,” said Dr William Zoghbi, director of the Methodist DeBakey Heart and Vascular Centre’s cardiovascular imaging institute.

Some damp squibs

Scipio was the brightest spot among otherwise disappointing cardiac stem cell results. The National Institutes of Health-backed Time trial found that bone marrow-derived stem cells delivered to heart muscles three or seven days after a myocardial infarction did not improve left ventricular function six months following the procedure, a finding confirmed by the Swiss-AMI trial.

That finding could have implications for future directions of research, Dr Zoghbi notes, as the more laborious effort to harvest cardiac tissue and grow stem cells in the Scipio trial has proved to have greater effect. “It looks like from the other trials of earlier versus later [infusion] there wasn’t really much of an advantage of [earlier] timing for bone marrow for stem cells.”

Meanwhile, the Poseidon trial comparing autologous and allogeneic bone marrow-derived cells documented few differences in safety outcomes between the two groups, and, importantly, found no significant autoimmune reaction among the patients treated with allogeneic stem cells, meaning that their use should not necessarily be ruled out at this early stage of research.

The Japanese Alcadia trial mirrored Scipio in its use of cardiac-derived cells, and shows signs of promise, but with six patients and just 24 weeks of follow-up it remains a stem cell experiment to watch closely.

The research that has been completed so far has given investigators direction, but has not yet come up with a single answer to how to use stem cells in cardiac regeneration, Dr Becker said. "The hard parts we still need to be thinking about carefully [are] when should the stem cells be administered? Should it be early or should it be the sub-acute stage?” he cautioned.

“Second is what kind of cell should it be? There are lots of different types of stem cells. Third is what are some of the homing signals [of cardiovascular damage] so the cells know to go to the right place and in that environment they can be taken up and become fully functional."

But he remained optimistic, saying: “I believe that regenerative medicine across the broad spectrum including the heart is still an area that we should study.”

Study Trial ID
Scipio NCT00474461
Time NCT00684021
Swiss-AMI NCT00355186
Posiedon NCT01087996
Alcadia NCT00981006

To contact the writer of this story email Jonathan Gardner in Los Angeles at jonathang@epvantage.com

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