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Updated: Apr 21, 2026
Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment
Published on: May 25, 2020
Stem cell factor gene transfer improves cardiac function after myocardial infarction in swine
Kiyotake Ishikawa1, Kenneth Fish2, Jaume Aguero2
1From the Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY (K.I., K.F., J.A., E.Y.-G., D.J., C.K., L.T., L.F., L.L., K.D.C., R.J.H.); Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)-Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain (J.A.); David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge (A.A.E., D.G.A.); and Celladon Corporation, San Diego, CA (K.Z.). kiyotake.ishikawa@mssm.edu.
Gene transfer of stem cell factor (SCF) improved cardiac function after myocardial infarction (MI) in pigs. SCF therapy enhanced ejection fraction and promoted angiogenesis, offering a potential treatment for ischemic cardiomyopathy.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Gene Therapy
Background:
- Stem cell factor (SCF) is a cytokine crucial for cell survival and migration, with elevated expression post-myocardial infarction (MI).
- SCF's role in cardiac repair after MI suggests potential therapeutic applications.
- Investigating SCF gene transfer for improving cardiac function post-MI is warranted.
Purpose of the Study:
- To evaluate the efficacy of gene transfer of membrane-bound human stem cell factor (SCF) in a large animal model of myocardial infarction (MI).
- To determine if SCF gene therapy can improve cardiac function and promote cardiac repair post-MI.
Main Methods:
- A transmural MI was induced in Yorkshire pigs.
- Pigs received intramyocardial injections of adenovirus encoding SCF (Ad.SCF) or β-gal (Ad.β-gal) in the infarct border zone.
- Cardiac function, cell recruitment, apoptosis, and capillary density were assessed at 3 months post-MI.
Main Results:
- Ad.SCF therapy significantly increased ejection fraction by 12% compared to baseline, while Ad.β-gal treatment decreased it.
- Preload-recruitable stroke work was significantly higher in the Ad.SCF group, indicating enhanced cardiac function.
- Histology revealed increased c-kit(+) cell recruitment, reduced apoptosis, and increased capillary density in Ad.SCF treated pigs.
Conclusions:
- Local SCF overexpression acutely recruits c-kit(+) cells to the infarct border zone post-MI.
- SCF gene transfer demonstrates significant improvements in cardiac function in a preclinical model of ischemic cardiomyopathy.
- SCF gene therapy holds promise for treating ischemic heart disease by enhancing cardiac repair and function.
