L-arginine from elder human mesenchymal stem cells induces angiogenesis and enhances therapeutic effects on ischemic heart diseases  

作　　者：Jian-Zhong Li Xu Zhan Hao-Bo Sun Chao Chi Guo-Fu Zhang Dong-Hui Liu Wen-Xi Zhang Li-Hua Sun Kai Kang 

机构地区：[1]Department of Cardiovascular Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China [2]Key Laboratory of Cell Transplantation of the National Ministry of Public Health,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China [3]Department of Thoracic Surgery,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710014,Shaanxi Province,China [4]Department of Cardiovascular Surgery,The First Affiliated Hospital of Harbin Medical University and Pharmacology Department of Pharmacy College of Harbin Medical University,Harbin Medical University,Harbin 150081,Heilongjiang Province,China [5]Key Laboratory of Hepatosplenic Surgery,Ministry of Education,Harbin 150001,Heilongjiang Province,China

出　　处：《World Journal of Stem Cells》2025年第4期79-98,共20页世界干细胞杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.82472147;the Key Research and Development Program of Heilongjiang Province of China,No.2023ZX06C04;the Open Fund of Key Laboratory of Hepatosplenic Surgery,Ministry of Education,Harbin,China,No.GPKF202402.

摘　　要：BACKGROUND Mesenchymal stem cell(MSC)-based therapy may be a future treatment for myocardial infarction(MI).However,few studies have assessed the therapeutic efficacy of adipose tissue-derived MSCs(ADSCs)obtained from elderly patients in comparison to that of bone marrow-derived MSCs(BMSCs)from the same elderly patients.The metabolomics results revealed a significantly higher Larginine excretion from aged ADSCs vs BMSCs in hypoxic conditions.This was hypothesized as the possible mechanism that ADSCs showed an improved angiogenic capacity and enhanced the therapeutic effect on ischemic heart diseases.AIM To investigate the role of L-arginine in enhancing angiogenesis and cardiac protection by comparing ADSCs and BMSCs in hypoxic conditions for MI therapy.METHODS Metabolomic profiling of supernatants from ADSCs and BMSCs under hypoxic conditions were performed.Then,arginine succinate lyase(ASL)overexpression and short hairpin RNA plasmid were prepared and transfected into BMSCs.Subsequently,in vitro wound healing and Matrigel tube formation assays were used to verify the proangiogenetic effects of ADSC positive control,BMSCs,BMSCs ASL short hairpin RNA,BMSCs ASL overexpressed,and BMSC negative control on cocultured human umbilical vein endothelial cells.All sample sizes,which were determined to meet the statistical requirements and be greater than 3,were established on the basis of previously established literature standards.The protein levels of vascular endothelial growth factor(VEGF),basic fibroblast growth factor,etc.were detected.In vivo,the five types of cells were transplanted into the infarcted area of MI rat models,and the therapeutic effects of the transplanted cells were evaluated by echocardiography on cardiac function and by Masson’s staining/terminal-deoxynucleotidyl transferase mediated nick end labeling assay/immunofluorescence detection on the infarcted area.RESULTS Metabolomic analysis showed that L-arginine was increased.Using ASL gene transfection,we upregulated the production of L-arginine in

关 键 词：Adipose tissue-derived mesenchymal stem cells Bone marrow-derived mesenchymal stem cells L-ARGININE METABOLIC ANGIOGENESIS AGING 

分 类 号：R54[医药卫生—心血管疾病]