Monday, December 17, 2007

Stem cell session overview highlights what future trials need

Stem cell session overview highlights what future trials need


The rising number of scientific publications on cardiac stem cell repair and the extraordinary emergence of public interest on the subject necessitate a forum for separating hype from reality, said Paul W. Armstrong, M.D., professor of medicine, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.

Dr. Armstrong spoke at a Late-Breaking Clinical Trials session on the final day of Scientific Sessions 2007, and offered some observations on the state of stem cell therapy in the early stages of research.

Dr. Armstrong first commented on the three stem-cell research papers presented in this session. In general, he said he was not satisfied he understood the nature of some studies’ comparative groups. Background therapies were not always clear and he could not tell that safety endpoints were always achieved. Improved LV function may indeed be the result of stem cell therapy, through myocardial regeneration, by preventing apoptosis and ventricular remodeling, or through paracrine effects, Dr. Armstrong said. “It could also be due to spontaneous improvement in LV function, medical therapy or to the revascularization,” he said. “Without considering these phenomenon, we have to be very careful about attribution of efficacy associated with stem cell therapy.”

Dr. Armstrong listed four essential questions he said must be answered as stem cell research in cardiovascular disease moves forward:

• What is the life span and destination of cells?

• Does methodology provide and maintain the effective surviving cell population?

• What is cell phenotype at the beginning and end — is there potential for transdifferentiation?

• Do paracrine effects exist?

Dr. Armstrong cited a report on stem cell research that suggests what such trials will need to further the science.

The European Society of Cardiology 2006 Consensus Task Force consensus report said preliminary trial findings suggest that the intracoronary route for cells harvested from bone marrow aspirates is efficacious, Dr. Armstrong said.

The European experts said there is also a need for consensus on surrogate markers and a need to standardize outcomes. “But outcomes studies need to recruit about 1,000 patients to provide adequate statistical power,” Dr. Armstrong said.

Where is stem cell research headed?

“Stem cell research: Quo vadis?” Dr. Armstrong asked, answering his Latinate question with four points:

• Trials must be randomized, blinded, placebo-controlled and adequately sized.

• Standardizing processing procedures of autologous stem/progenitor cells is imperative.

• Trials will need robust endpoints of efficacy and safety, adequately addressed.

• Follow-up must be complete and of adequate duration.

Be wary of comparing trials

Gerd Hasenfuss, M.D., professor, Faculty of Medicine, Gottingen University, Gottingen, Germany, emphasized the differences among the three stem cell trials presented at Scientific Sessions, suggesting that few generalizations can be made yet.

Dr. Hasenfuss urged observers to be aware that these three trials used two different stem cell populations.

In the IM-BMC randomized, double-blind trial, presented by Heikki Huikuri, M.D., lead investigator and professor of medicine and director of cardiology sector at the University of Oulu Hospital in Oulu, Finland, bone marrow cells were used.

Bone marrow cells were also delivered IM or IC to treat scarred myocardium in the IC/IM-BMC trial, a study of 63 patients reported by Manuel Galiñanes, M.D., lead author and professor of cardiac surgery in the cardiac surgery unit, Department of Cardiovascular Sciences at the University of Leicester, Leicester, United Kingdom.

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