Future Looks Bright for Stem Cell-Based Myocardial Therapy

MIAMI BEACH, FLA.—The clinical application of stem cells is feasible and safe in the setting of cardiac regeneration and repair to prevent and treat heart failure, according to Francisco Fernandez-Aviles, MD, PhD, of the Hospital General Universitario Gregorio Marañon, in Madrid, Spain. During a presentation at TCT 2012, he described how stem cells may be used in the future  in this setting.

Supporting evidence

Preclinical data in large animal models show embryonic cells can repair infarcted myocardium, and bone marrow stem cells are beneficial in LVEF. Additionally, data from phase 1 and phase 2 clinical trials have shown stem cells are valuable in certain cardiac conditions, though most trials have focused almost exclusively on ischemic heart disease. When categorizing these trials according to clinical setting, two different groups are defined: the use of stem cells in patients with STEMI and in those with chronic infarction and ischemia, LV dysfunction or both.

In STEMI, results suggest almost exclusively that bone marrow-derived cells can be used with a catheter-based method of delivery, Fernandez-Aviles said, according to data from 50 randomized controlled trials of 2,600 patients. Overall, no cardiac or extra-cardiac complications (short- and long-term) and better LV and clinical outcomes were reported.

For chronic infarction with ischemia, LV dysfunction or both, data on more than 800 patients from 11 heterogeneous phase 1 and phase 2 trials demonstrated treatment is safe, except in the presence of transient arrhythmias with myoblasts. Benefit was observed in angina symptoms, exercise capacity and ischemia, with modest or no benefit in LV function.

“If we have to summarize the efficacy of cells in cardiac repair, we can say there are many unexplored cardiac conditions, and bone marrow cells are better than conventional therapy in preventing post-infarction remodeling,” Fernandez-Aviles said. “There is a favorable effect on chronic ischemia and LV dysfunction in patients with viability and there are no benefits in terminal or preterminal HF.”

Looking ahead

According to Fernandez-Aviles, it is important to optimize cells to increase the modest effect in patients with LV, without terminal, dysfunction. “Will there be a role for cells in this terminal or preterminal situation? I think yes, but with the condition of the combined use of two strategies: more potent and more intelligent cells and a combination of cells with a nature of bioengineering,” he said. “We will have better cells every day; this is the case for cardiac stem cells in humans.”

Induced pluripotent stem cells will probably be the best cells achievable in the future, he said, noting that the discovery of these cells resulted in the Nobel Prize in Physiology or Medicine this year, which was awarded to John B. Gurdon, PhD, of Cambridge University in London and Shinya Yamanaka, PhD, of Kyoto University in Japan.

However, nothing can be accomplished if the extracellular structure of cells has been destroyed, Fernandez-Aviles said. In that case, the cell will need a new 3-D scaffold, either artificial or bioartificial. Currently, he and his colleagues are working on a project called Scaffolds and Bioartificial Organs for Transplantation (SABIO), which is focused on the creation of bioartifical scaffolds and organs from human and animal cadaveric hearts. They are working in collaboration with the Spanish National Transplant Organization and Doris Taylor, PhD, at the University of Minnesota, Minneapolis.

From May 2010 to August 2012, the project processed 45 human hearts using Taylor’s decellularization technique to eliminate cells in 72 hours. They obtained scaffolds with no cells, while preserving extracellular macrostructure, microvasculature and perfusion.

“We are now trying to study the biocompatibility of different cells integrated in these batches of scaffolds and create a transplantable patch made with cadaveric scaffolds and repopulated with receptor cells,” Fernandez-Aviles said. “Also, with the idea of creating, in the future in humans, a heart like the one created in the mouse by Doris Taylor.”