ESC Heart Failure (Feb 2024)
Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
Abstract
Abstract Aims There are few studies on the treatment of heart failure by injecting stem cells into the pericardial cavity. Can the cells injected into the pericardial cavity migrate through the epicardium to the myocardial tissue? Whether there is therapeutic effect and the mechanism of therapeutic effect are still unclear. This study investigated the therapeutic efficacy and evidence of cell migration of adipose‐derived stem cells (ADSCs) injected into the pericardial cavity in rat heart failure. The aim of this study is to demonstrate the effectiveness and mechanism of treating heart failure by injecting stem cells into the pericardial cavity, laying an experimental foundation for a new approach to stem cell therapy for heart disease in clinical practice. Methods and results The inguinal adipose tissue of male SD rats aged 4–6 weeks was taken, ADSCs were isolated and cultured, and their stem cell surface markers were identified. Forty rats aged 6–8 weeks were divided into sham operation group, heart failure group, and treatment group; there were 15 rats in the heart failure group and 15 rats in the treatment group. The heart failure model was established by intraperitoneal injection of adriamycin hydrochloride. The heart function of the three groups was detected by small animal ultrasound. The model was successful if the left ventricular ejection fraction < 50%. The identified ADSCs were injected into the pericardial cavity of rats in the treatment group. The retention of transplanted cells in pericardial cavity was detected by small animal in vivo imaging instrument, and the migration of transplanted cells into myocardial tissue was observed by tissue section and immunofluorescence. Western blotting and immunohistochemical staining were used to detect brain natriuretic peptide (BNP), α‐smooth muscle actin (α‐SMA), and C‐reactive protein (CRP). ADSCs express CD29, CD44, and CD73. On the fourth day after injection of ADSCs into pericardial cavity, they migrated to myocardial tissue through epicardium and gradually diffused to deep myocardium. The cell density in the pericardial cavity remains at a high level for 10 days after injection and gradually decreases after 10 days. Compared with the heart failure group, the expression of BNP and α‐SMA decreased (P < 0.05 and P < 0.001, respectively), and the expression of CRP in the treatment group was higher than that in the heart failure group (P < 0.0001). A small amount of BNP, α‐SMA, and CRP was expressed in the myocardium of the sham operation group. After injection of ADSCs, interleukin‐6 in myocardial tissue was significantly lower than that in heart failure myocardium (P < 0.01). After treatment, vascular endothelial growth factor A was significantly higher than that of heart failure (P < 0.01). Conclusions Pericardial cavity injected ADSCs can penetrate the epicardium, migrate into the myocardium, and have a therapeutic effect on heart failure. Their mechanism of action is to exert therapeutic effects through anti‐inflammatory, anti‐fibrosis, and increased angiogenesis.
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