Generation of Novel Reporter Stem Cells and Their Application for Molecular Imaging of Cardiac-Differentiated Stem Cells In Vivo

    Authors

    R. K. Kammili; D. G. Taylor; J. X. Xia; K. Osuala; K. Thompson; D. R. Menick;S. N. Ebert

    Comments

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    Abbreviated Journal Title

    Stem Cells Dev.

    Keywords

    TERATOMA FORMATION; GENE-EXPRESSION; HEART; CARDIOMYOCYTES; MYOCARDIUM; THERAPY; TRANSPLANTATION; REGENERATION; ENGRAFTMENT; PROGENITOR; Cell & Tissue Engineering; Hematology; Medicine, Research &; Experimental; Transplantation

    Abstract

    Stem cell therapies offer the potential for repair and regeneration of cardiac tissue. To facilitate evaluation of stem cell activity in vivo, we created novel dual-reporter mouse embryonic stem (mES) cell lines that express the firefly luciferase (LUC) reporter gene under the control of the cardiac sodium-calcium exchanger-1 (Ncx-1) promoter in the background of the 7AC5-EYFP mES cell line that constitutively expresses the enhanced yellow fluorescent protein (EYFP). We compared the ability of recombinant clonal cell lines to express LUC before and after induction of cardiac differentiation in vitro. In particular, one of the clonal cell lines (Ncx-1-43LUC mES cells) showed markedly enhanced LUC expression (45-fold increase) upon induction of cardiac differentiation in vitro. Further, cardiac differentiation in these cells was perpetuated over a period of 2-4 weeks after transplantation in a neonatal mouse heart model, as monitored by noninvasive bioluminescence imaging (BLI) and confirmed via postmortem immunofluorescence and histological assessments. In contrast, transplantation of undifferentiated pluripotent Ncx-1-43LUC mES cells in neonatal hearts did not result in detectable levels of cardiac differentiation in these cells in vivo. These results suggest that prior induction of cardiac differentiation in vitro enhances development and maintenance of a cardiomyocyte-like phenotype for mES cells following transplantation into neonatal mouse hearts in vivo. We conclude that the Ncx-1-43LUC mES cell line is a novel tool for monitoring early cardiac differentiation in vivo using noninvasive BLI.

    Journal Title

    Stem Cells and Development

    Volume

    19

    Issue/Number

    9

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    1437

    Last Page

    1448

    WOS Identifier

    WOS:000281517700016

    ISSN

    1547-3287

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