title: Enhancement of cell adhesion, retention, and survival of HUVEC/cbMSC aggregates that are transplanted in ischemic tissues by concurrent delivery of an antioxidant for therapeutic angiogenesis.
abstract: A recurring obstacle in cell-base strategies for treating ischemic diseases is the significant loss of viable cells that is caused by the elevated levels of regional reactive oxygen species (ROS), which ultimately limits therapeutic capacity. In this study, aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs), which are capable of inducing therapeutic angiogenesis, are prepared. We hypothesize that the concurrent delivery of an antioxidant N-acetylcysteine (NAC) may significantly increase cell retention following the transplantation of HUVEC/cbMSC aggregates in a mouse model with hindlimb ischemia. Our in vitro results demonstrate that the antioxidant NAC can restore ROS-impaired cell adhesion and recover the reduced angiogenic potential of HUVEC/cbMSC aggregates under oxidative stress. In the animal study, we found that by scavenging the ROS generated in ischemic tissues, NAC is likely to be able to establish a receptive cell environment in the early stage of cell transplantation, promoting the adhesion, retention, and survival of cells of engrafted aggregates. Therapeutic angiogenesis is therefore enhanced and blood flow recovery and limb salvage are ultimately achieved. The combinatory strategy that uses an antioxidant and HUVEC/cbMSC aggregates may provide a new means of boosting the therapeutic efficacy of cell aggregates for the treatment of ischemic diseases.
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Chieh-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC; Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Pan
authors.affiliation: Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tseng
authors.affiliation: Healthy Aging Research Center, Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Nuclear Medicine and Center of Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Yi-Pei
authors.initials: YP
authors.lastname: Yang
authors.affiliation: Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Tsai
authors.affiliation: Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, ROC.
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yen
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Division of Cardiovascular Surgery, Chiayi Branch, Veterans General Hospital-Taichung, Chiayi, Taiwan, ROC. Electronic address: weihaoji@vghtc.gov.tw.
authors.forename: Hao-Ji
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC. Electronic address: hwsung@mx.nthu.edu.tw.
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002448:Cell Adhesion; D002470:Cell Survival; D017690:Cell Transplantation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: Antioxidant; Cell therapy; Ischemic diseases; Oxidative stress; Reactive oxygen species