Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model  

作　　者：Ok-Hee Kim Ha-Eun Hong Haeyeon Seo Bong Jun Kwak Ho Joong Choi Kee-Hwan Kim Joseph Ahn Sang Chul Lee Say-June Kim 

机构地区：[1]Catholic Central Laboratory of Surgery,Institute of Biomedical Industry,College of Medicine,the Catholic University of Korea,Seoul 06591,South Korea [2]Department of Surgery,Division of Hepato-biliary Pancreatic Surgery,Seoul St.Mary’s Hospital,College of Medicine,the Catholic University of Korea,Seoul 06591,South Korea [3]Department of Surgery,Uijeongbu St.Mary's Hospital,College of Medicine,the Catholic University of Korea,Seoul 11765,South Korea [4]Department of Surgery,Daejeon St.Mary’s Hospital,College of Medicine,The Catholic University of Korea,Seoul 34943,South Korea

出　　处：《World Journal of Stem Cells》2020年第1期70-86,共17页世界干细胞杂志（英文版）（电子版）

基　　金：Supported by National Research Foundation of Korea,No.NRF-2015R1C1A1A02036931

摘　　要：BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the naïve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected to opBACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers) released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA) and generated the TAA-induced secretome(TAA-isecretome) after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2) inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase) compared to the na?ve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected t

关 键 词：Adipose-derived stem cells Disease-specificity Mesenchymal stem cells SECRETOME Peroxiredoxin-1 THIOACETAMIDE Toxic hepatic failure 

分 类 号：R73[医药卫生—肿瘤]