Graphene oxide flakes as a cellular adhesive: prevention of reactive oxygen species mediated death of implanted cells for cardiac repair.
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.
†School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
Jooyeon
J
Park
Bokyoung
B
Kim
†School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
Jin
J
Han
Jaewon
J
Oh
⊥Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.
Subeom
S
Park
§Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.
Seungmi
S
Ryu
Subin
S
Jung
†School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
Jung-Youn
JY
Shin
Beom Seob
BS
Lee
⊥Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea.
Byung Hee
BH
Hong
Donghoon
D
Choi
†School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.|§Interdisciplinary Program of Bioengineering, Seoul National University, Seoul 151-744, Republic of Korea.|∥Bio-MAX Institute, Institute of Chemical Processes, Seoul National University, Seoul 151-744, Republic of Korea.
Byung-Soo
BS
Kim
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000601:surgery; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D010087:Oxides; D017382:Reactive Oxygen Species; D006108:Graphite
anoikis; cell implantation; graphene oxide; myocardial infarction; reactive oxygen species