Characterization of long-term cultured c-kit+ cardiac stem cells derived from adult rat hearts

Shinka Miyamoto, Nanako Kawaguchi, Georgina M Ellison, Rumiko Matsuoka, Toshiharu Shin'oka, Hiromi Kurosawa

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    97 Citations (Scopus)

    Abstract

    Previous studies have revealed c-kit-positive (c-kit(+)) cardiac stem cells (CSCs) in the adult mammalian heart and these cells could be a suitable cell source for heart regeneration therapy. However, these cells have not been fully evaluated in terms of characterization and effect of long-term culture, which is necessary for their safe and optimal usage. Therefore, we isolated c-kit(+) CSCs from adult rat hearts to characterize these cells and investigate stability over long-term culture. We performed isolations of c-kit(+) CSCs 11 times and passaged them 40 times in a bulk culture system; we termed these cultures, bulk culture CSCs (CSC-BC). c-kit(+) CSCs expressed stemness genes and exhibited stem cell properties of single cell-derived clone formation, cardiosphere generation, and potential to differentiate into the three main cardiac lineages: cardiomyocyte, smooth muscle, and endothelial cells in vitro. Over long-term culture, some CSC-BC up-regulated GATA-4 expression, which resulted in enhanced cardiomyocyte differentiation, suggesting that the GATA-4 high c-kit(+) CSCs have potent cardiac regenerative potential. We also observed the spontaneous differentiation into cells other than cardiac lineages, such as adipocyte and skeletal myocyte. This effect of long-term culture on the c-kit(+) CSCs has not been previously reported. Interestingly, when c-kit(+) CSCs were co-cultured with adult rat cardiomyocytes, we found increased cardiomyocyte survival, and the growth factors, insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF), appeared to be responsible factors. The present study suggests that c-kit(+) CSCs have great therapeutic potential yet should be further investigated and optimized as a cell source for regenerative therapies prior to transplantation.
    Original languageEnglish
    Pages (from-to)105-16
    Number of pages12
    JournalSTEM CELLS AND DEVELOPMENT
    Volume19
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Keywords

    • Animals
    • Rats, Inbred Lew
    • Age Factors
    • Rats, Transgenic
    • Adult Stem Cells
    • Proto-Oncogene Proteins c-kit
    • Cell Culture Techniques
    • Cell Differentiation
    • Cell Separation
    • Cell Proliferation
    • Rats
    • Muscle Fibers, Skeletal
    • Cells, Cultured
    • Adipocytes
    • Rats, Wistar
    • Time Factors
    • Myocytes, Cardiac
    • Myocardium

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