Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts Through SCF--c-kit and SDF-1--CXCR4 Signaling Axes
Advisor:
Yau, Terrence M
Department:
Medical Science
Issue Date:
Jun-2014
Abstract (summary):
Objective: We investigated the roles of stem cell factor (SCF)–c-kit and stromal derived factor-1 (SDF-1)–CXCR4 signaling in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted mesenchymal stem cells (MSCs) in infarcted hearts.
Methods: 3 weeks after LAD ligation, female Lewis rats underwent 10-channel needle TMR, followed by daily IV injections of 1-million male donor MSCs for 5 days, either wild type (WT) or with knockdown of c-kit or CXCR4. Three days and 1 week after transplantation, we evaluated MSC engraftment, SCF—c-kit and SDF-1—CXCR4 expression, and left ventricular (LV) function.
Results: MSC engraftment was affected by both TMR and donor cell type at 3 days and 1 week. LV ejection fraction improved when WT MSCs were infused, but knockdown of either receptor abrogated TMR-mediated augmentation of MSC reparative effect.
Conclusions: Downregulation of either c-kit or CXCR4 on MSC decreased engraftment of circulating MSC and inhibited reparative effects of TMR.
Permanent Link:
https://hdl.handle.net/1807/72545
Content Type:
Thesis
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