Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients With Hypoplastic Left Heart Syndrome

Abstract

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P =0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P =0.049), improved somatic growth ( P =0.0005), reduced heart failure status ( P =0.003), and lower incidence of coil occlusion for collaterals ( P =0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01273857.

CD34+ Cell Transplantation Improves Right Ventricular Function in Patients with Nonischemic Dilated Cardiomyopathy

“…In these infants, cardiosphere‐derived cell therapy was associated with a significant improvement in RV ejection fraction and reduced BNP levels 23. In accordance with these findings, data from the present study suggest that cell therapy may also represent an effective therapeutic intervention to improve RV function in adult chronic heart failure population.…”

Perspective on Congenital Heart Disease Research

“…Examples of these technologies include biological pacemakers to treat surgical heart block, tissue-engineered conduits that grow with the patient, and stem cell therapy to improve right ventricular function in patients with hypoplastic left heart syndrome. 8 Although cure of CHD is a valiant goal with a distant horizon, it is one we should keep in our sights. Gene or gene product alteration, through genome editing, gene therapy, or RNA interference, has shown promise for being able to significantly correct monogenic diseases in animal models.…”

Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

“…Even in clinical trials, structural and functional parameters, carried out by several imaging techniques, remain as conventional endpoints. A significant part of the clinical trials do not resort to any kind of molecular monitoring [81][82][83][84]88,89,92,94] and when they do, they are limited to some conventional cardiac markers (Table 1), mainly BNP [90,96], NT-proBNP [77][78][79][80]86,87,91,93], in addition to creatine kinase [77,86,87,90,[95][96][97], troponins I [90,96,97] and T [77,80,86,87] and some inflammation markers, such as TNF-α, IL-6 [79] and C-reactive protein [77,86]. Therefore, we suggest to screen biofluids (Box 5, Fig.…”