The incidence of heart failure (HF) continues to grow despite advances to current therapies which are effective insofar as slowing disease progression. Cardiac stem cell (CSC) therapy is an emerging treatment for the reversal of HF. We sought to examine the effect of genetically engineering CSCs to over-express stromal cell-derived factor 1α (SDF1α) on myocardial repair. SDF1α over-expressing CSCs exhibited a broader paracrine signature resulting in increased stimulation of capillary network formation and chemotaxis under in vitro conditions. Using a murine model of myocardial ischemia, we demonstrated over-expression of SDF1α increased myocardial SDF1α content, reduced scar burden and increased activation of PI3K/AKT signaling as compared to non-transduced CSC and vehicle controls. These effects improved cardiac function without increasing cell engraftment suggesting that the mechanisms driving these benefits are largely paracrine mediated. Taken together this data suggests that transplantation of CSCs genetically programmed to over-express SDF1α provides superior cardiac repair by boosting the content of cardio-protective cytokines during the critical healing phase after myocardial infarction.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/31723 |
| Date | January 2014 |
| Creators | Tilokee, Everad |
| Contributors | Davis, Darryl |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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