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Updated: May 10, 2026
The Isolation and Culture of Primary Epicardial Cells Derived from Human Adult and Fetal Heart Specimens
Published on: April 24, 2018
Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy
Hadhami Hamdi1, Solène Emmanuelle Boitard, Valérie Planat-Benard
1Inserm U, Laboratory of Biosurgical Research, Paris, France.
Insights
Epicardial delivery of adipose tissue-derived stroma cell (ADSC) sheets stabilized cardiac function and reduced fibrosis in a mouse model of non-ischaemic dilated cardiomyopathy, suggesting potential for cell therapy in heart failure.
Area of Science:
- Cardiology
- Regenerative Medicine
- Biomaterials Science
Background:
- Non-ischaemic cardiomyopathies are a significant cause of heart failure.
- Global cell delivery strategies are hypothesized to be optimal for these conditions.
- Adipose tissue-derived stroma cells (ADSCs) offer potential therapeutic benefits.
Purpose of the Study:
- To assess the efficacy of epicardially delivered ADSC sheets in a mouse model of dilated cardiomyopathy.
- To investigate the impact of cell therapy on cardiac function, remodeling, and fibrosis.
- To evaluate cell fate and engraftment after transplantation.
Main Methods:
- A cardiac-specific, tamoxifen-inducible model of dilated cardiomyopathy was used in mice.
- ADSC sheets were cultured on temperature-responsive polymers and transplanted onto the epicardium.
- Cardiac function was assessed by echocardiography, and histological analyses were performed.
- Green fluorescent protein (GFP)-labeled ADSCs were used to track cell fate.
Main Results:
- ADSC sheet application stabilized left ventricular fractional shortening compared to controls.
- Epicardial cell therapy prevented adverse left ventricular remodeling.
- Reduced expression of cardiac stress markers and decreased myocardial fibrosis were observed in treated mice.
- Engraftment of ADSCs in the epicardium and myocardium was confirmed.
Conclusions:
- Epicardially delivered cell-seeded biomaterials demonstrate functional relevance in non-ischaemic heart failure.
- ADSC sheets represent a promising therapeutic approach for dilated cardiomyopathy.
- This study supports further investigation into cell-based therapies for cardiac regeneration.
Aims:
Few studies have assessed the effects of cell therapy in non-ischaemic cardiomyopathies which, however, contribute to a large number of cardiac failures. Assuming that such conditions are best suited for a global delivery of cells, we assessed the effects of epicardially delivered adipose tissue-derived stroma cell (ADSC) sheets in a mouse model of dilated cardiomyopathy based on cardiac-specific and tamoxifen-inducible invalidation of serum response factor.
Methods And Results:
Three weeks after tamoxifen administration, the function of the left ventricle (LV) was assessed by echocardiography. Twenty-nine mice were then allocated to control (n = 9, non-transgenic), sham (n = 10, transgenic non-treated), and treated (n = 10, transgenic) groups. In the treated group, 3 × 10(6) allogeneic ADSCs were cultured for 2 days onto temperature-responsive polymers and the generated sheets were then transplanted over the surface of the heart. In 10 additional mice, the sheet was made of green fluorescent protein (GFP)-labelled ADSCs to track cell fate. Function, engraftment, and fibrosis were blindly assessed after 3 weeks. In the non-treated group, fractional shortening declined compared with baseline, whereas the sheet application resulted in its stabilization. This correlated with a lesser degree of LV remodelling, as LV end-diastolic and end-systolic diameters did not differ from baseline values. Many GFP(+) cells were identified in the epicardial graft and in the myocardium. Treated animals also displayed a reduced expression of the stress-induced atrial natriuretic factor and beta-myosin heavy chain genes. These protective effects were also accompanied by a reduction of myocardial fibrosis.
Conclusion:
These results strongly suggest the functional relevance of epicardially delivered cell-seeded biomaterials to non-ischaemic heart failure.
