Combination of mesenchymal stem cells and three-dimensional collagen scaffold preserves ventricular remodeling in rat myocardial infarction model  

作　　者：Rida-e-Maria Qazi Irfan Khan Kanwal Haneef Tuba Shakil Malick Nadia Naeem Waqas Ahmad Asmat Salim Sadia Mohsin 

机构地区：[1]Stem Cell Laboratory,Dr.Panjwani Center for Molecular Medicine and Drug Research,ICCBS,University of Karachi,Karachi 75270,Sindh,Pakistan [2]Dr.Zafar H.Zaidi Center for Proteomics,University of Karachi,Karachi 75270,Sindh,Pakistan [3]Dow Research Institute of Biotechnology and Biomedical Sciences(DRIBBS),Dow University of Health and Sciences,Ojha Campus,Karachi 74200,Sindh,Pakistan [4]Cardiovascular Research Center,Lewis Katz School of Medicine,Temple University,Philadelphia,PA 19140,United States

出　　处：《World Journal of Stem Cells》2022年第8期633-657,共25页世界干细胞杂志（英文版）（电子版）

摘　　要：BACKGROUND Cardiovascular diseases are the major cause of mortality worldwide.Regeneration of the damaged myocardium remains a challenge due to mechanical constraints and limited healing ability of the adult heart tissue.Cardiac tissue engineering using biomaterial scaffolds combined with stem cells and bioactive molecules could be a highly promising approach for cardiac repair.Use of biomaterials can provide suitable microenvironment to the cells and can solve cell engraftment problems associated with cell transplantation alone.Mesenchymal stem cells(MSCs)are potential candidates in cardiac tissue engineering because of their multilineage differentiation potential and ease of isolation.Use of DNA methyl transferase inhibitor,such as zebularine,in combination with three-dimensional(3D)scaffold can promote efficient MSC differentiation into cardiac lineage,as epigenetic modifications play a fundamental role in determining cell fate and lineage specific gene expression.AIM To investigate the role of collagen scaffold and zebularine in the differentiation of rat bone marrow(BM)-MSCs and their subsequent in vivo effects.METHODS MSCs were isolated from rat BM and characterized morphologically,immunophenotypically and by multilineage differentiation potential.MSCs were seeded in collagen scaffold and treated with 3μmol/L zebularine in three different ways.Cytotoxicity analysis was done and cardiac differentiation was analyzed at the gene and protein levels.Treated and untreated MSC-seeded scaffolds were transplanted in the rat myocardial infarction(MI)model and cardiac function was assessed by echocardiography.Cell tracking was performed by DiI dye labeling,while regeneration and neovascularization were evaluated by histological and immunohistochemical analysis,respectively.RESULTS MSCs were successfully isolated and seeded in collagen scaffold.Cytotoxicity analysis revealed that zebularine was not cytotoxic in any of the treatment groups.Cardiac differentiation analysis showed more pronounced results in the type 3 tr

关 键 词：Mesenchymal stem cells Myocardial infarction Cardiac tissue engineering Demethylating agent Collagen scaffold ZEBULARINE 

分 类 号：R54[医药卫生—心血管疾病] R-332[医药卫生—内科学]