The purpose of this study was to identify conditioning strategies for mesenchymal stromal cells (MSC) which optimize cellular immunosuppressive potency. By identifying new treatment strategies and previously unidentified small molecules capable of stimulating MSC we hope to pave the way tailoring licensed MSC phenotypes to be used in a specific disease state, rather than a one size fits all package. We sought to determine how MSC act in response to a changing immune response or environmental condition. MSC are exquisitely sensitive to changes in their environmental conditions and we show that cellular transcriptome and secretome changes are conditionally responsive to their inflammatory stimulus. One of the main subjects of analysis here is the observations of how these cellular profiles evolve over time in the presence of an inflammatory environment. Similarly, this study observes how MSC behavior changes after an inflammatory event has been resolved to address, in part, the plasticity of MSC licensing and the ability of MSC to rapidly recall a previous immunosuppressive state upon secondary challenge with an inflammatory stimulus. Data was obtained from in vitro experiments with human bone marrow derived MSC and donor human peripheral blood mononuclear cells (PBMC), while in vivo data was obtained using C57BL6/J mice.
Overall this research demonstrated that MSC potency can be bolstered by small molecule and drug treatment conditioning, and that certain disease conditions may be more effectively paired with specific MSC conditioning strategies to improve their therapeutic effectiveness.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-7201 |
| Date | 01 August 2017 |
| Creators | Brown, Alex Joseph |
| Contributors | Ankrum, James A. |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | thesis |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright © 2017 Alex Joseph Brown |
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