Cardiopoietic Stem Cells Derived From Bone Marrow Pass Phase 2 Heart-Failure Test

April 12, 2013

AALST, BELGIUM — Bone-marrow–derived autologous cardiopoietic stem cells injected into the hibernating myocardium of patients with heart failure improves left ventricular ejection fraction as well as six-minute-walk test and quality-of-life scores, according to the results of a large, multicenter stem-cell–therapy trial[1].

There was no observed cardiac or systemic toxicity with the novel treatment.

Published April 11, 2013 in the Journal of the American College of Cardiology, the study is "the first application of guided stem cells for targeted regeneration of a failing organ," according to Dr Jozef Bartunek (OLV Hospital, Aalst, Belgium) and colleagues. "By introducing lineage guidance into the cell-therapy protocol, the C-CURE trial provides initial clinical evidence for a new approach in cardiovascular regenerative medicine."

Previous studies testing stem cells used bone-marrow stem cells in their lineage-unspecified state, the researchers explain. These trials were largely in the setting of acute MI. In contrast, the C-CURE study tested the safety and feasibility of stem-cell therapy in patients where distinct regenerative strategies are needed to "restore parenchymal integrity and prevent progressive remodeling."

In the present study, bone marrow was harvested from the patient's hip and isolated stem cells were treated with a protein cocktail to replicate cues of heart development. These cues were decoded using endoderm-mediated guidance of the mesoderm, a process that took coinvestigators Drs Atta Behfar and AndreTerzic (Mayo Clinic, Rochester, MN) and other researchers more than 10 years to understand and develop[2]. These cardiopoietic stem cells were then injected into the myocardium.

In total, 48 patients with heart failure were randomized in the phase 2 C-CURE study. Patients in the control arm received standard treatment, including a beta-blocker, ACE inhibitor/angiotensin-receptor blocker, and diuretic, while patients in the treatment arm received standard of care and the bone-marrow–derived cardiopoietic stem cells. At two years, no patient in the treatment arm stopped therapy because of an adverse event, and there was no evidence of uncontrolled tissue growth.

Regarding efficacy at six months, there was a statistically significant absolute 7% increase in left ventricular ejection fraction (from 27.5% to 34.5%; p<0.0001) in the stem-cell arm, while there was no change in patients receiving standard therapy. In addition, treatment with the cardiopoietic stem cells reduced end-systolic volume and end-diastolic volume as well as improved the six-minute-walk test (up from 394 m to 456 m; no change in the control arm) and other quality-of-life measurements.

"Improved left ventricular ejection fraction, as observed at six months in the present study, is a powerful predictor of beneficial cardiovascular outcome in heart failure and was here associated with reduced end-systolic volume consistent with reversal of pathologic remodeling," write Bartunek and colleagues.

Mayo Clinic partnered with Cardio3 Biosciences for product development, manufacturing, and clinical trial execution. Mayo Clinic and Terzic have a financial interest related to technology in this research program.

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