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Patiwet PhD Dissertation.pdf (3.25 MB)

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Mesenchymal Stem Cell Immunomodulation Effects as Determined by Cryo-imaging

Wuttisarnwattana, Patiwet
http://rave.ohiolink.edu/etdc/view?acc_num=case1427978566

Abstract Details

2015, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Existing imaging modalities for tracking cells in vivo have many limitations such as limited resolution or limited field of view. Cryo-imaging is the only imaging technology that enables cell tracking with single cell sensitivity throughout entire animals in small rodents. It provides cell detection anywhere in mice and determines cell densities far below that which can be observed with any other imaging technologies such as MRI, CT, PET, SPECT and BLI. Using the novel imaging and detection technologies, we explored therapeutic mechanisms of mesenchymal stem cell (MSC) in murine models of graft-versus-host disease (GVHD). Many investigators have found that intravascular infusion of exogenous MSCs improves outcomes of GVHD-induced animals. Although, at least 40 clinical trials are in progress, it is still unclear what the therapeutic mechanism is? In this study, the proposed working hypothesis is that the MSCs specifically go to secondary lymphoid organs (SLOs) in order to suppress alloreactive T-cells proliferation which eventually leads to the attenuation of GVHD. In this study, we show that the hypothesis is indeed the mechanism behind the scene and is testable using our proposed imaging technology and experiments. Firstly, we extended/optimized cryo-imaging technology to detect/analyze/visualize of fluorescently labeled cells (MSCs and T-cells). Secondly, we identified bio-distribution of MSCs in a GVHD mouse model. We found evidence showing that MSCs preferentially co-localize with the effector T-cells in the SLOs after intravenous infusion. Lastly, we observed that MSCs could suppress T-cells proliferation in vivo. Novel T-cell proliferation assays were established to study the effectiveness of the MSC therapy. The assays were developed based on SLO volume enlargement approach and CFSE dilution approach. This project is significant as we have developed a new, important technique for the study of stem cell bio-distribution with single cell sensitivity over an entire mouse, allowing one to answer the pervasive question, “Where did my cells go?” In addition, we applied the technology to aid determination of the underlying mechanism of MSC rescue on GVHD patients. We believe that our research can help pave the way to for many additional, important studies of stem cell therapy and regenerative medicine.
David Wilson, PhD (Committee Chair)
Kenneth Cooke, MD (Committee Member)
Andrew Rollins, PhD (Committee Member)
Vira Chankong, PhD (Committee Member)
Wouter van't Hof, PhD (Committee Member)
147 p.
Biomedical Engineering; Biomedical Research; Computer Science; Experiments; Immunology; Medical Imaging
stem cell; mesenchymal stem cell; bio-distribution; co-localization; cryo-imaging; fluorescent imaging; medical imaging; graft-versus-host disease; GVHD; cell detection; segmentation; 3D visualization; T-cell; T-cell proliferation; image processing

Recommended Citations

Citations

  • Wuttisarnwattana, P. (2015). Mesenchymal Stem Cell Immunomodulation Effects as Determined by Cryo-imaging [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1427978566

    APA Style (7th edition)

  • Wuttisarnwattana, Patiwet. Mesenchymal Stem Cell Immunomodulation Effects as Determined by Cryo-imaging. 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1427978566.

    MLA Style (8th edition)

  • Wuttisarnwattana, Patiwet. "Mesenchymal Stem Cell Immunomodulation Effects as Determined by Cryo-imaging." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1427978566

    Chicago Manual of Style (17th edition)

case1427978566
276
© 2015, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.