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

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4987-4999
Number of pages13
JournalACS Nano
Volume9
Issue number5
DOIs
Publication statusPublished - 2015 May 26

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Graphite
flakes
death
Oxides
Graphene
adhesives
Reactive Oxygen Species
Adhesives
graphene
Repair
stem cells
Stem cells
Oxygen
oxides
myocardial infarction
oxygen
ischemia
myocardium
implantation
cells

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Park, Jooyeon ; Kim, Bokyoung ; Han, Jin ; Oh, Jaewon ; Park, Subeom ; Ryu, Seungmi ; Jung, Subin ; Shin, Jung Youn ; Lee, Beom Seob ; Hong, Byung Hee ; Choi, Donghoon ; Kim, Byung Soo. / Graphene oxide flakes as a cellular adhesive : Prevention of reactive oxygen species mediated death of implanted cells for cardiac repair. In: ACS Nano. 2015 ; Vol. 9, No. 5. pp. 4987-4999.
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abstract = "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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Park, J, Kim, B, Han, J, Oh, J, Park, S, Ryu, S, Jung, S, Shin, JY, Lee, BS, Hong, BH, Choi, D & Kim, BS 2015, 'Graphene oxide flakes as a cellular adhesive: Prevention of reactive oxygen species mediated death of implanted cells for cardiac repair', ACS Nano, vol. 9, no. 5, pp. 4987-4999. https://doi.org/10.1021/nn507149w

Graphene oxide flakes as a cellular adhesive : Prevention of reactive oxygen species mediated death of implanted cells for cardiac repair. / Park, Jooyeon; Kim, Bokyoung; Han, Jin; Oh, Jaewon; Park, Subeom; Ryu, Seungmi; Jung, Subin; Shin, Jung Youn; Lee, Beom Seob; Hong, Byung Hee; Choi, Donghoon; Kim, Byung Soo.

In: ACS Nano, Vol. 9, No. 5, 26.05.2015, p. 4987-4999.

Research output: Contribution to journalArticle

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T2 - Prevention of reactive oxygen species mediated death of implanted cells for cardiac repair

AU - Park, Jooyeon

AU - Kim, Bokyoung

AU - Han, Jin

AU - Oh, Jaewon

AU - Park, Subeom

AU - Ryu, Seungmi

AU - Jung, Subin

AU - Shin, Jung Youn

AU - Lee, Beom Seob

AU - Hong, Byung Hee

AU - Choi, Donghoon

AU - Kim, Byung Soo

PY - 2015/5/26

Y1 - 2015/5/26

N2 - 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.

AB - 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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