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Author Notes:

Correspondence: Michael E. Davis, Ph.D., Department of Biomedical Engineering, Emory University, 1760 Haygood Drive, W200, Atlanta, Georgia 30322, USA. Telephone: 404-727-9858; E-Mail: michael.davis@bme.emory.edu

U.A.: conception and design, performance of research, data analysis and interpretation, manuscript writing, final approval of manuscript; A.W.S.: conception and design, performance of research, data analysis and interpretation; K.M.F., A.V.B., A.G., D.T., M.E.B., and M.S.

Performance of research; R.J.: performance of research, data analysis and interpretation; J.D.F., B.E.K., K.R.K., and B.A.: provision of study material or patients; M.B.W.: conception and design, manuscript writing;M.O.P.

Data analysis and interpretation; M.E.D.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.

The authors indicated no potential conflicts of interest.

Subjects:

Research Funding:

This work was supported by Grant HL124380 from the National Heart, Lung, and Blood Institute to M.E.D. and M.O.P., funds from the Center for Pediatric Nanomedicine at Children’s Healthcare of Atlanta, and the Darryll M. Ceccoli Research Fund with thanks to Katrina Ceccoli.

Research reported in this publication was also supported by the National Heart, Lung, and Blood Institute under award T32HL007745.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Cell Biology
  • Randomized phase 1 trial
  • Stem cells
  • Ventricular function
  • Follow up
  • Regeneration
  • Transplantation
  • Model
  • Cardiomyopathy
  • Cardiospheres
  • Delivery

Age-Dependent Effect of Pediatric Cardiac Progenitor Cells After Juvenile Heart Failure

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Journal Title:

Stem Cells: Translational Medicine

Volume:

Volume 5, Number 7

Publisher:

, Pages 883-892

Type of Work:

Article | Final Publisher PDF

Abstract:

Children with congenital heart diseases have increased morbidity and mortality, despite various surgical treatments, therefore warranting better treatment strategies. Here we investigate the role of age of human pediatric cardiac progenitor cells (hCPCs) on ventricular remodeling in a model of juvenile heart failure. hCPCs isolated from children undergoing reconstructive surgeries were divided into 3 groups based on age: neonate (1 day to 1month), infant (1month to 1 year), and child (1 to 5 years). Adolescent athymic rats were subjected to sham or pulmonary artery banding surgery to generate a model of right ventricular (RV) heart failure. Two weeks after surgery, hCPCs were injected in RV musculature noninvasively. Analysis of cardiac function4weekspost-transplantationdemonstratedsignificantly increased tricuspid annular plane systolic excursion and RV ejection fraction and significantly decreased wall thickness and fibrosis in rats transplanted with neonatal hCPCs compared with saline-injected rats. Computational modeling and systems biology analysis were performed on arrays and gave insights into potential mechanisms at the microRNA and gene level. Mechanisms including migration and proliferation assays, as suggested by computational modeling, showed improved chemotactic and proliferative capacity of neonatal hCPCs compared with infant/child hCPCs. In vivo immune staining further suggested increased recruitment of stem cell antigen 1-positive cells in the right ventricle. This is the first study to assess the role of hCPC age in juvenile RV heart failure. Interestingly, the reparative potential of hCPCs is age-dependent, with neonatal hCPCs exerting the maximum beneficial effect compared with infant and child hCPCs.

Copyright information:

© AlphaMed Press 2016

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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