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Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart
Tohru Hosoyama1, Makoto Samura2, Tomoaki Kudo2
1Department of Surgery and Clinical Science, Yamaguchi University Graduate School of MedicineUbe, Japan; Center for Regenerative Medicine, Yamaguchi University Graduate School of MedicineUbe, Japan.
American Journal of Translational Research
|February 18, 2016
Summary
Hypoxic preconditioning improves cardiosphere-derived cell (CDC) sheets for myocardial infarction therapy. Preconditioned CDC sheets enhance heart function and reduce scarring, offering a promising cell-based treatment strategy.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Therapy
Background:
- Cardiosphere-derived cells (CDCs) show promise for myocardial infarction (MI) treatment.
- Poor cell retention limits the efficacy of current CDC therapies.
- Cell sheet technology improves graft cell retention but requires further optimization.
Purpose of the Study:
- To investigate the impact of hypoxic preconditioning on the therapeutic efficacy of CDC monolayer sheets.
- To determine if hypoxia priming enhances CDC retention and function in infarcted hearts.
- To evaluate the potential of combining cell sheet technology with hypoxic preconditioning for ischemic heart disease.
Main Methods:
- CDC monolayer sheets were subjected to hypoxic preconditioning (2% oxygen for 24 hours).
- Preconditioned and normoxic CDC sheets were implanted into mouse models of chronic myocardial infarction.
- Vascular endothelial growth factor (VEGF) expression was assessed via the PI3-kinase/Akt pathway.
- Left ventricular function and cardiac fibrosis were evaluated post-implantation.
Main Results:
- Hypoxic preconditioning significantly upregulated VEGF expression in CDC sheets through the PI3-kinase/Akt pathway.
- Implantation of preconditioned CDC sheets led to improved left ventricular function in infarcted hearts.
- Preconditioned CDC sheets demonstrated reduced cardiac fibrosis compared to normoxic controls.
- Therapeutic outcomes were superior with hypoxic preconditioned CDC sheets versus normoxic CDC sheets.
Conclusions:
- Hypoxic preconditioning enhances the therapeutic potential of CDC sheets for myocardial infarction.
- Preconditioned CDC sheets exhibit augmented angiogenic and anti-fibrotic activities.
- Combining cell sheet technology with hypoxic preconditioning presents a viable therapeutic strategy for treating chronic infarcted hearts.
