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Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart
S Sundararaman1, T J Miller, J M Pastore
1Skirball Laboratory for Cardiovascular Cellular Therapeutics, Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Gene Therapy
|April 8, 2011
Summary
Non-viral gene transfer of stromal cell-derived factor-1 alpha (SDF-1) effectively improved cardiac function in rats with ischemic cardiomyopathy. This approach promoted angiogenesis and scar remodeling, offering a new strategy for heart failure treatment.
Area of Science:
- Cardiovascular Biology
- Gene Therapy
- Regenerative Medicine
Background:
- Stromal cell-derived factor-1 alpha (SDF-1) has shown promise in improving cardiac function post-myocardial infarction (MI).
- Previous studies utilized cell therapy for SDF-1 delivery, necessitating exploration of alternative methods like gene transfer.
Purpose of the Study:
- To investigate the efficacy of non-viral gene transfer of human SDF-1 (hSDF-1) using naked plasmid DNA to improve cardiac function in a rodent model of ischemic cardiomyopathy.
- To optimize plasmid delivery systems for enhanced in vivo expression of hSDF-1.
Main Methods:
- Tested SDF-1 and luciferase plasmids with different promoters (CMV with/without enhancers, pMHC) in a rat model of heart failure one month after MI.
- Assessed in vivo gene expression levels and duration, cardiac function (fractional shortening), and cardiac tissue characteristics (vessel density, fibrosis).
Main Results:
- Plasmid constructs with cytomegalovirus enhancer (pCMVe) demonstrated a 10-fold greater in vivo expression than pCMV or pMHC promoters, sustained over 30 days.
- Direct injection of pCMVe-hSDF1 significantly increased fractional shortening by 24.97% at 4 weeks post-injection, unlike control or pMHC-hSDF1 groups.
- Immunohistochemistry revealed increased vessel density and a trend toward decreased myocardial fibrosis in hSDF-1 treated hearts.
Conclusions:
- Stand-alone non-viral gene transfer of hSDF-1 is a viable strategy for improving cardiac function in ischemic cardiomyopathy.
- Optimized plasmid design (pCMVe-hSDF1) enhances gene expression and therapeutic effect, promoting angiogenesis and beneficial cardiac remodeling.
