Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells

Daheui Choi, Hwankyu Lee, Hyun Bum Kim, Miso Yang, Jiwoong Heo, Younsun Won, Seung Soon Jang, Jong Kuk Park, Youngsook Son, Tong In Oh, Eunah Lee, Jinkee Hong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Intravenous administration of mesenchymal stem cells (MSCs) has served as a clinical intervention for inflammatory diseases. Once entered to blood circulation, MSCs are exposed to a harsh environment which sharply decreases cell viability due to the fact that injected cells, being susceptible to shear stress, are subjected to the high velocities of the bloodstream and lack of proper mechanical support that keeping them in an attachment-deprived state. Here, we coated the nanofilm onto viable MSCs by depositing poly-l-lysine and hyaluronic acid molecules along with arginine-glycine-aspartic acid (RGD peptide) as building blocks to protect cells from shear stress and stabilize them in a single cell, suspension state. In this article, we found that nanofilm-coated cells showed significantly increased cell survival in vitro and in vivo, which was also supported by the activation of survival-related protein, Akt. The coated nanofilm did not interfere with the stemness of MSCs which was determined based on the colony forming unit-fibroblast (CFU-F) assay and in vitro differentiation potential. Because of the characteristics of films showing light molecular deposition density, flexibility, and looseness, application of nanofilms did not block cell migration. When the cells were administrated intravenously, the nanofilm coated MSCs not only prolonged blood circulation lifetime but also showed increased stem cell recruitment to injured tissues in the muscle injury in vivo model, due to prolonged survival. Surface modification of MSCs using nanofilms successfully modulated cell activity enabling them to survive the anoikis-inducing state, and this can provide a valuable tool to potentiate the efficacy of MSCs for in vivo cell therapy.

Original languageEnglish
Pages (from-to)2055-2065
Number of pages11
JournalChemistry of Materials
Volume29
Issue number5
DOIs
Publication statusPublished - 2017 Mar 14

Fingerprint

Stem cells
Peptides
Surface treatment
Hemodynamics
Shear stress
Cells
Hyaluronic acid
Arginine
arginyl-glycyl-aspartic acid
Hyaluronic Acid
Fibroblasts
Aspartic Acid
Glycine
Lysine
Muscle
Amino acids
Assays
Suspensions
Chemical activation
Tissue

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Materials Chemistry

Cite this

Choi, Daheui ; Lee, Hwankyu ; Kim, Hyun Bum ; Yang, Miso ; Heo, Jiwoong ; Won, Younsun ; Jang, Seung Soon ; Park, Jong Kuk ; Son, Youngsook ; Oh, Tong In ; Lee, Eunah ; Hong, Jinkee. / Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells. In: Chemistry of Materials. 2017 ; Vol. 29, No. 5. pp. 2055-2065.
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Choi, D, Lee, H, Kim, HB, Yang, M, Heo, J, Won, Y, Jang, SS, Park, JK, Son, Y, Oh, TI, Lee, E & Hong, J 2017, 'Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells', Chemistry of Materials, vol. 29, no. 5, pp. 2055-2065. https://doi.org/10.1021/acs.chemmater.6b04096

Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells. / Choi, Daheui; Lee, Hwankyu; Kim, Hyun Bum; Yang, Miso; Heo, Jiwoong; Won, Younsun; Jang, Seung Soon; Park, Jong Kuk; Son, Youngsook; Oh, Tong In; Lee, Eunah; Hong, Jinkee.

In: Chemistry of Materials, Vol. 29, No. 5, 14.03.2017, p. 2055-2065.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells

AU - Choi, Daheui

AU - Lee, Hwankyu

AU - Kim, Hyun Bum

AU - Yang, Miso

AU - Heo, Jiwoong

AU - Won, Younsun

AU - Jang, Seung Soon

AU - Park, Jong Kuk

AU - Son, Youngsook

AU - Oh, Tong In

AU - Lee, Eunah

AU - Hong, Jinkee

PY - 2017/3/14

Y1 - 2017/3/14

N2 - Intravenous administration of mesenchymal stem cells (MSCs) has served as a clinical intervention for inflammatory diseases. Once entered to blood circulation, MSCs are exposed to a harsh environment which sharply decreases cell viability due to the fact that injected cells, being susceptible to shear stress, are subjected to the high velocities of the bloodstream and lack of proper mechanical support that keeping them in an attachment-deprived state. Here, we coated the nanofilm onto viable MSCs by depositing poly-l-lysine and hyaluronic acid molecules along with arginine-glycine-aspartic acid (RGD peptide) as building blocks to protect cells from shear stress and stabilize them in a single cell, suspension state. In this article, we found that nanofilm-coated cells showed significantly increased cell survival in vitro and in vivo, which was also supported by the activation of survival-related protein, Akt. The coated nanofilm did not interfere with the stemness of MSCs which was determined based on the colony forming unit-fibroblast (CFU-F) assay and in vitro differentiation potential. Because of the characteristics of films showing light molecular deposition density, flexibility, and looseness, application of nanofilms did not block cell migration. When the cells were administrated intravenously, the nanofilm coated MSCs not only prolonged blood circulation lifetime but also showed increased stem cell recruitment to injured tissues in the muscle injury in vivo model, due to prolonged survival. Surface modification of MSCs using nanofilms successfully modulated cell activity enabling them to survive the anoikis-inducing state, and this can provide a valuable tool to potentiate the efficacy of MSCs for in vivo cell therapy.

AB - Intravenous administration of mesenchymal stem cells (MSCs) has served as a clinical intervention for inflammatory diseases. Once entered to blood circulation, MSCs are exposed to a harsh environment which sharply decreases cell viability due to the fact that injected cells, being susceptible to shear stress, are subjected to the high velocities of the bloodstream and lack of proper mechanical support that keeping them in an attachment-deprived state. Here, we coated the nanofilm onto viable MSCs by depositing poly-l-lysine and hyaluronic acid molecules along with arginine-glycine-aspartic acid (RGD peptide) as building blocks to protect cells from shear stress and stabilize them in a single cell, suspension state. In this article, we found that nanofilm-coated cells showed significantly increased cell survival in vitro and in vivo, which was also supported by the activation of survival-related protein, Akt. The coated nanofilm did not interfere with the stemness of MSCs which was determined based on the colony forming unit-fibroblast (CFU-F) assay and in vitro differentiation potential. Because of the characteristics of films showing light molecular deposition density, flexibility, and looseness, application of nanofilms did not block cell migration. When the cells were administrated intravenously, the nanofilm coated MSCs not only prolonged blood circulation lifetime but also showed increased stem cell recruitment to injured tissues in the muscle injury in vivo model, due to prolonged survival. Surface modification of MSCs using nanofilms successfully modulated cell activity enabling them to survive the anoikis-inducing state, and this can provide a valuable tool to potentiate the efficacy of MSCs for in vivo cell therapy.

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