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Graphene oxide flakes as a cellular adhesive: prevention of reactive oxygen species mediated death of implanted cells for cardiac repair

 Jooyeon Park  ;  Bokyoung Kim  ;  Jin Han  ;  Jaewon Oh  ;  Subeom Park  ;  Seungmi Ryu  ;  Subin Jung  ;  Jung-Youn Shin  ;  Beom Seob Lee  ;  Byung Hee Hong  ;  Donghoon Choi  ;  Byung-Soo Kim 
 ACS NANO, Vol.9(5) : 4987-4999, 2015 
Journal Title
Issue Date
Animals ; Cell Adhesion/drug effects ; Cell Death/drug effects ; Cell Survival/drug effects ; Graphite/chemistry ; Graphite/pharmacology* ; Humans ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/drug effects* ; Myocardial Reperfusion Injury/pathology ; Myocardial Reperfusion Injury/surgery ; Myocardium/metabolism ; Myocardium/pathology* ; Oxides/chemistry* ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism*
anoikis ; cell implantation ; graphene oxide ; myocardial infarction ; reactive oxygen species
Mesenchymal stem cell (MSC) implantation has emerged as a potential therapy for myocardial infarction (MI). However, the poor survival of MSCs implanted to treat MI has significantly limited the therapeutic efficacy of this approach. This poor survival is primarily due to reactive oxygen species (ROS) generated in the ischemic myocardium after the restoration of blood flow. ROS primarily causes the death of implanted MSCs by inhibiting the adhesion of the MSCs to extracellular matrices at the lesion site (i.e., anoikis). In this study, we proposed the use of graphene oxide (GO) flakes to protect the implanted MSCs from ROS-mediated death and thereby improve the therapeutic efficacy of the MSCs. GO can adsorb extracellular matrix (ECM) proteins. The survival of MSCs, which had adhered to ECM protein-adsorbed GO flakes and were subsequently exposed to ROS in vitro or implanted into the ischemia-damaged and reperfused myocardium, significantly exceeded that of unmodified MSCs. Furthermore, the MSC engraftment improved by the adhesion of MSCs to GO flakes prior to implantation enhanced the paracrine secretion from the MSCs following MSC implantation, which in turn promoted cardiac tissue repair and cardiac function restoration. This study demonstrates that GO can effectively improve the engraftment and therapeutic efficacy of MSCs used to repair the injury of ROS-abundant ischemia and reperfusion by protecting implanted cells from anoikis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Beom Seob(이범섭)
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
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