BACKGROUND: Human cardiac stem cells (CSCs) promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of CSCs in very young patients with nonischemic 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 2 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 with adult-derived CDCs. Last, neonatal-derived CDCs were more cardiomyogenic than adult-derived CDCs when cocultured with neonatal cardiomyocytes and displayed enhanced angiogenic function compared with adult-derived CDCs. CONCLUSIONS: Neonatal-derived CDCs have a strong regenerative ability when compared with 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.
BACKGROUND:Human cardiac stem cells (CSCs) promote myocardial regeneration in adult ischemic myocardium. The regenerative capacity of CSCs in very young patients with nonischemic 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 2 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 with adult-derived CDCs. Last, neonatal-derived CDCs were more cardiomyogenic than adult-derived CDCs when cocultured with neonatal cardiomyocytes and displayed enhanced angiogenic function compared with adult-derived CDCs. CONCLUSIONS: Neonatal-derived CDCs have a strong regenerative ability when compared with 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.
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Authors: Junya Takagawa; Yan Zhang; Maelene L Wong; Richard E Sievers; Neel K Kapasi; Yan Wang; Yerem Yeghiazarians; Randall J Lee; William Grossman; Matthew L Springer Journal: J Appl Physiol (1985) Date: 2007-03-08
Authors: Stefan Koudstaal; Sanne J Jansen Of Lorkeers; Roberto Gaetani; Johannes M I H Gho; Frebus J van Slochteren; Joost P G Sluijter; Pieter A Doevendans; Georgina M Ellison; Steven A J Chamuleau Journal: Stem Cells Transl Med Date: 2013-05-08 Impact factor: 6.940
Authors: Philip D Tatman; Kathleen C Woulfe; Anis Karimpour-Fard; Danielle A Jeffrey; James Jaggers; Joseph C Cleveland; Karin Nunley; Matthew Rg Taylor; Shelley D Miyamoto; Brian L Stauffer; Carmen C Sucharov Journal: JCI Insight Date: 2017-07-20