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Secondary sphere formation enhances the functionality of cardiac progenitor cells. | LitMetric

AI Article Synopsis

  • Loss of heart cells after a heart attack affects heart function, but recent research shows that cardiac stem cells might help repair the damage.
  • A new method called repeated sphere formation was tested, which improves the quality and ability of these progenitor cells while growing them in a 3D culture instead of traditional 2D cultures.
  • When these improved cells were transplanted into damaged heart tissue, they not only integrated well but also significantly improved heart function and promoted the growth of new blood vessels, suggesting a potential strategy for cardiac repair that could also apply to other stem cell therapies.

Article Abstract

Loss of cardiomyocytes impairs cardiac function after myocardial infarction (MI). Recent studies suggest that cardiac stem/progenitor cells could repair the damaged heart. However, cardiac progenitor cells are difficult to maintain in terms of purity and multipotency when propagated in two-dimensional culture systems. Here, we investigated a new strategy that enhances potency and enriches progenitor cells. We applied the repeated sphere formation strategy (cardiac explant → primary cardiosphere (CS) formation → sphere-derived cells (SDCs) in adherent culture condition → secondary CS formation by three-dimensional culture). Cells in secondary CS showed higher differentiation potentials than SDCs. When transplanted into the infarcted myocardium, secondary CSs engrafted robustly, improved left ventricular (LV) dysfunction, and reduced infarct sizes more than SDCs did. In addition to the cardiovascular differentiation of transplanted secondary CSs, robust vascular endothelial growth factor (VEGF) synthesis and secretion enhanced neovascularization in the infarcted myocardium. Microarray pathway analysis and blocking experiments using E-selectin knock-out hearts, specific chemicals, and small interfering RNAs (siRNAs) for each pathway revealed that E-selectin was indispensable to sphere initiation and ERK/Sp1/VEGF autoparacrine loop was responsible for sphere maturation. These results provide a simple strategy for enhancing cellular potency for cardiac repair. Furthermore, this strategy may be implemented to other types of stem/progenitor cell-based therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437578PMC
http://dx.doi.org/10.1038/mt.2012.109DOI Listing

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