An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats  

作　　者：Jialu Yao Junlang Li Dashuai Zhu Yuan Li Panagiotis Tasoudis Shuo Liu Xuan Mei Kristen Popowski Thomas G.Caranasos Haipeng Wang Mingzhu Xu Tingbo Jiang Kan Shen Hongxia Li Ke Huang 

机构地区：[1]Department of Cardiology,The First Affiliated Hospital of Soochow University,Suzhou,215000,China [2]Department of Molecular Biomedical Sciences,NC State University,Raleigh,NC,USA [3]Joint Department of Biomedical Engineering,University of North Carolina Chapel Hill and North Carolina State University,Raleigh,NC,USA [4]Division of Cardiothoracic Surgery,University of North Carolina at Chapel Hill,Chapel Hill,NC,USA [5]Division of Engineering in Medicine,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Cambridge,MA,02139,USA [6]Department of Critical Care Medicine,Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital,Shanghai,China

出　　处：《Bioactive Materials》2024年第10期571-581,共11页生物活性材料（英文）

基　　金：supported by the American Heart Association(21CDA855570 to KH);JY is supported by Suzhou Youth Science and Technology Project(KJXW2023012 to JY);the Natural Science Foundation of Jiangsu Province(BK20231198);the Jiangsu Province Health Care Development Special Fund(M2022038)。

摘　　要：Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation.To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF,we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive(MISA)that could be delivered locally through an endoscope-guided intrapericardial injection.To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients,we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections.In vitro,we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability,but also inhibited their apoptosis.In vivo,we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation,angiogenesis,and mitochondrial respiration.Additionally,we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system.In general,our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

关 键 词：Secretomes Cardiac stromal cells Extracellular matrix Chemotherapy Heart failure Intrapericardial injection 

分 类 号：R541.6[医药卫生—心血管疾病]