Abstract
Background—Human stem cells (CSCs) promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of CSCs in the very young patients with non-ischemic congenital heart defects has not been explored. We hypothesized that isolated neonatal-derived CSCs may have a higher regenerative ability than adult-derived CSCs and might address the structural deficiencies of congenital heart disease.
Methods and Results—Human specimens were obtained during routine cardiac surgical procedures from right atrial appendage tissue discarded from two age groups: neonates and adults patients. We developed a reproducible isolation method that generated cardiosphere derived cells (CDCs), regardless of starting tissue weight or age. Neonatal-derived CDCs demonstrated increased number of cardiac progenitor cells expressing c-kit+, flk-1 and Islet-1 by flow cytometry and immunofluorescence. When transplanted into infarcted myocardium, neonatal-derived CDCs had a significantly higher ability to preserve myocardial function, prevent adverse remodeling and enhance blood vessel preservation and/or formation when compared to adult CDCs. Lastly, neonatal-derived CDCs were more cardiomyogenic than adult CDCs when co-cultured with neonatal cardiomyocytes and displayed enhanced angiogenic function compared to adult CDCs.
Conclusions—Neonatal-derived CDCs have a strong regenerative ability when compared to adult-derived CDCs that may depend on angiogenic cytokines and an increase prevalence of stem cells. This has important implications in the potential use of CDCs in future clinical trials.
David L. Simpson, PhD1,*, Rachana Mishra, PhD1,*, Sudhish Sharma, PhD1, Saik Kia Goh, BS1, Savitha Deshmukh, MS1, and Sunjay Kaushal, MD, PhD21Division of Cardiothoracic Surgery, Children’s Memorial Hospital, Chicago IL, USA2Division of Cardiac Surgery, University of Maryland, Baltimore, MD USA
Published in final edited form as:Circulation. 2012 September 11; 126(11 Suppl 1): S46–S53. doi:10.1161/CIRCULATIONAHA.111.084699.