Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure

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...

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Main Authors: Wenjing Guo, Yaping Xu, Xinyi Liu, Jintao Dou, Zhikun Guo
Format: Article
Language:English
Published: Wiley 2024-02-01
Series:ESC Heart Failure
Subjects:
Online Access:https://doi.org/10.1002/ehf2.14606
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author Wenjing Guo
Yaping Xu
Xinyi Liu
Jintao Dou
Zhikun Guo
author_facet Wenjing Guo
Yaping Xu
Xinyi Liu
Jintao Dou
Zhikun Guo
author_sort Wenjing Guo
collection DOAJ
description 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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spelling doaj.art-9f74857bbb864d1090eb35a8aae6caf52024-01-23T08:40:25ZengWileyESC Heart Failure2055-58222024-02-0111149250210.1002/ehf2.14606Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failureWenjing Guo0Yaping Xu1Xinyi Liu2Jintao Dou3Zhikun Guo4Henan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University 601 Jinsui Road Xinxiang Henan ChinaHenan Provincial Key Laboratory of Heart Reconstruction and Transplantation Zhengzhou Cardiovascular Hospital Zhengzhou Henan ChinaHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University 601 Jinsui Road Xinxiang Henan ChinaHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University 601 Jinsui Road Xinxiang Henan ChinaHenan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical University 601 Jinsui Road Xinxiang Henan ChinaAbstract 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.https://doi.org/10.1002/ehf2.14606Atrial natriuretic peptideα‐Smooth muscle actinCRPAdipose‐derived stem cellsPericardial injectionHeart failure model
spellingShingle Wenjing Guo
Yaping Xu
Xinyi Liu
Jintao Dou
Zhikun Guo
Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
ESC Heart Failure
Atrial natriuretic peptide
α‐Smooth muscle actin
CRP
Adipose‐derived stem cells
Pericardial injection
Heart failure model
title Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
title_full Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
title_fullStr Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
title_full_unstemmed Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
title_short Therapeutic effect of adipose‐derived stem cells injected into pericardial cavity in rat heart failure
title_sort therapeutic effect of adipose derived stem cells injected into pericardial cavity in rat heart failure
topic Atrial natriuretic peptide
α‐Smooth muscle actin
CRP
Adipose‐derived stem cells
Pericardial injection
Heart failure model
url https://doi.org/10.1002/ehf2.14606
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