Abstract
Background—We sought to determine the location, expression, and characterization of cardiac stem cells (CSCs) in children with end-stage heart failure (ESHF). We hypothesized ESHF myocardium would contain an increased number of CSCs relative to age-matched healthy myocardium, and ESHF-derived CSCs would have diminished functional capacity as evidenced by reduced telomere length.
Methods—Tissue samples were obtained from the explanted hearts of children undergoing heart transplantation with ESHF, defined as New York Heart Association class III or IV and ejection fraction less than 0.20, and from age-matched congenital heart disease patients with normal myocardium. The expression profile of cardiac-specific stem cell markers was determined using quantitative real time polymerase chain reaction and immunofluorescence. Cardiac stem cell growth reserve was assessed with telomere length.
Results—There were 15 ESHF and 15 age-matched congenital heart disease patients. End-stage heart failure myocardium demonstrated increased expression of c-kit+ and islet-1+ CSCs by 2.0- and 2.5-fold, respectively, compared with myocardium from congenital heart disease patients. There was no difference in expression of c-kit+ CSCs with advancing age from infants to children in ESHF myocardium. The c-kit+ CSCs isolated from ESHF patients demonstrated significantly reduced telomere length, suggesting a diminished functional capability in these cells (8.1 ± 0.6 kbp versus 6.3 ± 0.3 kbp; p = 0.015).
Conclusions—End-stage heart failure myocardium demonstrated an age-independent increase in CSCs relative to healthy myocardium; however, these CSCs from ESHF patients may have diminished proliferative ability and reduced functionality as an autologous cell therapy candidate. Further investigation is necessary to determine the role of ESHF-derived CSCs within the myocardium.
Brody Wehman, MD, Sudhish Sharma, PhD, Rachana Mishra, PhD, Yin Guo, PhD, Evan J. Colletti, PhD, Zachary N. Kon, MD, Srinivasa Raju Datla, PhD, Osama T. Siddiqui, MD, Keerti Balachandran, MS, and Sunjay Kaushal, MD, PhDDivision of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland
Published in final edited form as:Ann Thorac Surg. 2015 August ; 100(2): 615–622. doi:10.1016/j.athoracsur.2015.04.088.