Exogenous migratory therapy : investigating ex vivo-derived dendritic cell migration and delivery of anti-inflammatory therapy after stroke
Abstract/Contents
- Abstract
- Stroke is the fourth leading cause of death in industrialized countries and is a major cause of disability in the United States. Protein therapy shows promise for the reduction of brain damage following stroke; however, current delivery methods lack the ability to efficiently deliver therapeutic proteins to the brain without invasive methods. It is possible to exploit normal inflammation in the brain, and the resultant immune cell migration following stroke, by injecting modified leukocytes such as dendritic cells that act as carriers of protective transgenes in a non-invasive, ischemia-targeted manner. With this solution in mind, my thesis focused on investigating the mechanisms of ex vivo-derived dendritic cell (exDC) migration to the stroke brain and using exDCs as vehicles for the delivery of anti-inflammatory proteins. I determined that the number of exDCs that migrate to the brain after stroke is positively correlated with the level of inflammation 6 hour after stroke. Tissue damage is also positively correlated with inflammation at this same time point. Finally, I investigated whether exDCs could be modified to deliver anti-inflammatory therapy after stroke. ExDCs were successfully transduced to constitutively express soluble TNF receptor 1 (sTNFR1) secrete functional protein that does not alter the phenotype or migratory ability of the cells. Importantly, when sTNFR1-exDCs are delivered after stroke they reduce inflammation and damage in vivo. These studies indicate that the use of cell-mediated protein delivery may be a promising new approach to reduce brain damage following acute neurological insult.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Works, Melissa Gale |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Sapolsky, Robert M |
| Thesis advisor | Sapolsky, Robert M |
| Thesis advisor | McConnell, Susan K |
| Thesis advisor | Michie, Sara |
| Thesis advisor | Wyss-Coray, Anton |
| Advisor | McConnell, Susan K |
| Advisor | Michie, Sara |
| Advisor | Wyss-Coray, Anton |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Melissa Gale Works. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2013. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Melissa Gale Works
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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