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Updated: Aug 5, 2025
Author Spotlight: Enhancing Coronary Artery Revascularization
Published on: September 15, 2023
An Adjuvant Stem Cell Patch with Coronary Artery Bypass Graft Surgery Improves Diastolic Recovery in Porcine
Rishav Aggarwal1, Koray N Potel2, Annie Shao1
1Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Insights
Mesenchymal stem cells (MSCs) therapy during coronary artery bypass graft (CABG) surgery improved diastolic function in hibernating myocardium. MSCs reduced inflammation and fibrosis, offering a potential new treatment for heart dysfunction.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Diastolic dysfunction persists after coronary artery bypass graft (CABG) surgery in patients with hibernating myocardium (HIB).
- Myocardial HIB is characterized by ischemia without infarction, leading to impaired cardiac function.
- Current treatments often fail to fully restore diastolic function in these patients.
Purpose of the Study:
- To investigate if adjunctive mesenchymal stem cells (MSCs) therapy during CABG surgery improves diastolic function in HIB.
- To determine if MSCs reduce myocardial inflammation and fibrosis, key contributors to diastolic dysfunction.
- To explore the underlying mechanisms, including changes in peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) and inflammatory signaling.
Main Methods:
- Juvenile swine models of HIB were created by constricting the left anterior descending (LAD) artery.
- CABG surgery was performed using a left-internal-mammary-artery (LIMA)-to-LAD graft, with or without an epicardial MSC-embedded patch.
- Cardiac magnetic resonance imaging (MRI) and tissue analysis (fibrosis, inflammation, PGC1α) were conducted post-surgery.
Main Results:
- Diastolic function was significantly reduced in HIB swine compared to controls.
- CABG with adjunctive MSC treatment significantly improved diastolic function.
- MSCs treatment decreased inflammation, fibrosis, and increased PGC1α levels, suggesting reduced oxidant stress and myofibroblast presence.
Conclusions:
- Adjunctive MSC therapy during CABG can improve diastolic function in patients with hibernating myocardium.
- MSC treatment mitigates myocardial inflammation and fibrosis, potentially through modulating oxidant stress and inflammatory pathways.
- This cell-based approach offers a promising strategy for enhancing recovery after CABG in specific cardiac conditions.
Abstract:
Diastolic dysfunction persists despite coronary artery bypass graft surgery (CABG) in patients with hibernating myocardium (HIB). We studied whether the adjunctive use of a mesenchymal stem cells (MSCs) patch during CABG improves diastolic function by reducing inflammation and fibrosis. HIB was induced in juvenile swine by placing a constrictor on the left anterior descending (LAD) artery, causing myocardial ischemia without infarction. At 12 weeks, CABG was performed using the left-internal-mammary-artery (LIMA)-to-LAD graft with or without placement of an epicardial vicryl patch embedded with MSCs, followed by four weeks of recovery. The animals underwent cardiac magnetic resonance imaging (MRI) prior to sacrifice, and tissue from septal and LAD regions were collected to assess for fibrosis and analyze mitochondrial and nuclear isolates. During low-dose dobutamine infusion, diastolic function was significantly reduced in HIB compared to the control, with significant improvement after CABG + MSC treatment. In HIB, we observed increased inflammation and fibrosis without transmural scarring, along with decreased peroxisome proliferator-activated receptor-gamma coactivator (PGC1α), which could be a possible mechanism underlying diastolic dysfunction. Improvement in PGC1α and diastolic function was noted with revascularization and MSCs, along with decreased inflammatory signaling and fibrosis. These findings suggest that adjuvant cell-based therapy during CABG may recover diastolic function by reducing oxidant stress-inflammatory signaling and myofibroblast presence in the myocardial tissue.
