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Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts

Colon-Jimenez, Lisandra
http://rave.ohiolink.edu/etdc/view?acc_num=osu1266171874

Abstract Details

2010, Master of Science, Ohio State University, Biomedical Engineering.
Therapeutic administration of bone marrow derived progenitor cells (BMPC) to infarcted hearts produced promising yet inconsistent results. The goal of this study was to understand the factors limiting cell therapy with BMPC from both, a biochemical and biomechanical perspective. First, we evaluated the effect of oxygen on survival of isolated mouse CD117/c-Kit+ BMPC using the annexin V-propidium iodide assay in flow cytometry. The data showed an intrinsic resistance of these cells to hypoxic conditions, even at longer incubation times. Direct exposure of isolated c-Kit+ BMPC to peroxynitrite (PxN) induced their apoptosis in a time- and concentration- dependent manner, possibly due to a protein modification. One-dimensional western blotting showed a nitrotyrosine-containing band of approximately 83 kDa in cells exposed to the PxN donor, SIN-1, for 20 min and maintained in ambient oxygen. Two-dimensional western blotting revealed a major nitrated band, as well as few satellites. These findings suggest that even though many proteins have tyrosine residues, only few are sensitive to the deleterious modifications induced by PxN. Finally, we studied the effect of size on an ex vivo model of beads perfused within a rat heart in Langendorff mode. The results showed increased retention of large beads (10µm) in the heart after coronary vasodilatation induced by sodium nitroprusside. Nevertheless, increasing elution in successive fractions was observed. In conclusion, ROS-derived nitration is a novel factor potentially limiting the survival of BMPC spontaneously recruited or isolated for administration into ischemic hearts. Geometrical factors, such as relative cell/microvessels size could play a key role in the retention of perfused progenitor cells. These results suggest that nitric oxide could become toxic for stem cells after an infarct when combining with the overly produced ROS. Although it could be beneficial to mediate blood vessel accessibility to circulating progenitor cells through its vasodilatation effect. Altogether, these observations proposed that a ROS-scavenging treatment (i.e. antioxidants) could improve the efficiency of BMPC therapy in patients with myocardial infarction.
Nicanor Moldovan, PhD (Advisor)
Mark Ruegsegger, PhD (Committee Member)
98 p.
Biology; Biomedical Research; Chemical Engineering; Engineering
cell therapy; bone marrow stem cells; redox stress; nitrotyrosine

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Citations

  • Colon-Jimenez, L. (2010). Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1266171874

    APA Style (7th edition)

  • Colon-Jimenez, Lisandra. Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts. 2010. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1266171874.

    MLA Style (8th edition)

  • Colon-Jimenez, Lisandra. "Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts." Master's thesis, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1266171874

    Chicago Manual of Style (17th edition)

osu1266171874
431
© 2010, some rights reserved.Creative Commons License Factors limiting spontaneous repair and their relevance for the efficiency of stem cell therapy of infarcted hearts by Lisandra Colon-Jimenez is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.