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Cell-cell and cell-medium interactions in the growth of mouse embryonic stem cells

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dc.contributor.advisor Joel Voldman and Alexander van Oudenaarden. en_US Mittal, Nikhil, 1979- en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Physics. en_US 2011-05-09T13:59:15Z 2011-05-09T13:59:15Z 2010 en_US 2010 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2010. en_US
dc.description This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. en_US
dc.description Cataloged from student-submitted PDF version of thesis. en_US
dc.description Includes bibliographical references (p. 100-108). en_US
dc.description.abstract Embryonic stem cells serve as powerful models for the study of development and disease and hold enormous potential for future therapeutics. Due to the potential for embryonic stem cells (ESCs) to provide a variety of tissues for use in regenerative medicine, there has been great interest in the identification of factors that govern the differentiation of ESCs into specific lineages. Much of this research builds on previous studies of the role of intercellular signaling in the specification of various cell types in the developing embryo. However, relatively little work has been done on understanding the role of cell-cell communication in the self-renewal of ESCs. In the first part of this thesis I describe the development and testing of new devices for studying intercellular signaling - the nDEP microwell array and the Bio Flip Chip (BFC). We used the BFC to show that cell-cell interaction improves the colony-forming efficiency and the self-renewal of mouse ESCs. Further, we demonstrate that the interaction is at least partly diffusible. In the next part of the thesis I describe our use of more traditional assays to validate the results obtained using the BFC and to further explore the role of diffusible signaling in the survival of mouse ESCs. We demonstrate the existence of an optimal density for 2-day culture of mouse ESCs. Further, we demonstrate that the increase in growth with plating density (103-104 cells/cm2) is at least partly due to the existence of one or more survival-enhancing autocrine factor(s) in mouse ESC cultures, and that one of these factors is Cyclophilin A. Finally, we demonstrate that changes in the low molecular weight composition of the medium are likely responsible for the decrease in growth at high plating densities (>104 cells/cm2). We use a numerical model to show that competition between the positive effect (on growth) of autocrine survival factors and the negative effect of nutrient depletion can account for the observed optimal growth density. Our study provides new insight into the processes underlying, and optimization of, growth in cell types that lack contact inhibition such as cancer cells and stem cells. en_US
dc.description.statementofresponsibility by Nikhil V. Mittal. en_US
dc.format.extent 130 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri en_US
dc.subject Physics. en_US
dc.title Cell-cell and cell-medium interactions in the growth of mouse embryonic stem cells en_US
dc.title.alternative Cell-cell and cell-medium interactions in the growth of mouse ESCs en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Physics. en_US
dc.identifier.oclc 713650794 en_US

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