C-CURE: Cardiopoietic stem cells show promise in HF patients

An international team of researchers reported that therapy with cardiopoietic stem cells was feasible, safe and associated with signals of benefit in patients with chronic HF.

This is the first application in patients of lineage-guided stem cells for targeted regeneration of a failing organ, researchers said.

The prospective, multicenter, phase 2 C-CURE trial included 48 patients with stable HF aged 18 to 75 years from Belgium, Serbia and Switzerland. Patients were randomly assigned standard care for HF in accordance with established guidelines (beta-blocker, ACE inhibitor, angiotensin receptor blocker, diuretic) or standard care plus cardiopoietic stem cell therapy. In the cell therapy group, bone marrow was harvested from the hip and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells were then delivered by endomyocardial injection guided by left ventricular electromechanical mapping, according to the study abstract.

Cell therapy vs. standard care

The primary endpoint was feasibility and safety at 2 years. According to results, mesenchymal stem cell cocktail-based priming was achieved for all patients with dose attained in 75%. The derived cardiopoietic stem cells were delivered without complications in 100% of cases. The researchers found no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy.

Six months after therapy, echocardiography revealed a 7% improvement in LV ejection fraction in the cell therapy group (27.5% to 34.5%), whereas in the standard care group LVEF was unchanged (27.8% to 28%; P<.0001 for comparison). Cell therapy was also associated with reduction in LV end-systolic volume of –24.8 mL compared with –8.8 mL in the standard care group (P<.001). The cell therapy group also had significant improvements in the 6-minute walk test, from 394 m to 456 m; walk test results decreased in the standard care group, from 419 m to 404 m (P<.01).

A post-hoc analysis, including composite clinical score integrating outcome measures, corroborated the benefits of cell therapy in this study.

Andre Terzic

“The benefit to patients who received cardiopoietic stem cell therapy was significant,” Andre Terzic, MD, PhD, director of the Mayo Clinic Center for Regenerative Medicine, Rochester, Minn., said in a press release.

Potential new treatment option

Jozef Bartunek, MD, PhD, from Cardiovascular Center Aalst, OLV Hospital, Belgium, and colleagues concluded that the C-CURE trial data introduce “a potential new treatment for HF using readily accessible bone marrow mesenchymal stem cells lineage-specified to upgrade cardioregenerative aptitude.”

In an accompanying editorial, Charles E. Murry, MD, PhD, professor in the department of pathology at University of Washington, and colleagues said these data compare favorably with the most potent therapies in HF.

“Harvesting marrow locally, shipping it to a central lab for processing and returning the expanded cells for injection is not a trivial undertaking, and the investigators achieved [an approximate] 70% overall success rate,” Murry and colleagues wrote. They added, the “improvement in EF is dramatic, particularly given the duration between ischemic injury and cell therapy.”

For more information:

Bartunek J. JAm Coll Cardiol. 2013;doi:10.1016/j.bbr.2011.03.031.

Murry CE. JAm Coll Cardiol. 2013;doi:10.1016/j.bbr.2011.03.031.

Disclosure: Bartunek reports contracted research between Cardiovascular Research Center Aalst and several pharmaceutical and device companies; Cardiovascular Research Center Aalst is co-founder of Cardio3 BioSciences. Murry and colleagues report no relevant financial disclosures. Terzic reports Mayo Clinic-administered research grants from the NIH and Cardio3 BioSciences; Mayo Clinic has rights to future royalties from Cardio3 BioSciences. See the full study for the other researchers’ relevant financial disclosures.