Genetically engineered myoblast sheet for therapeutic angiogenesis

Joan Lee, Indong Jun, Hyun Ji Park, Taek Jin Kang, Heungsoo Shin, Seung-Woo Cho

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis.

Original languageEnglish
Pages (from-to)361-372
Number of pages12
JournalBiomacromolecules
Volume15
Issue number1
DOIs
Publication statusPublished - 2014 Jan 13

Fingerprint

Vascular Endothelial Growth Factor A
Hydrogel
Hydrogels
Muscle
Nanoparticles
Tyramine
Assays
Esters
Polymers
Plasmids
Tissue
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Lee, Joan ; Jun, Indong ; Park, Hyun Ji ; Kang, Taek Jin ; Shin, Heungsoo ; Cho, Seung-Woo. / Genetically engineered myoblast sheet for therapeutic angiogenesis. In: Biomacromolecules. 2014 ; Vol. 15, No. 1. pp. 361-372.
@article{7c42315a244f4064b1ce4ed6b16c42e3,
title = "Genetically engineered myoblast sheet for therapeutic angiogenesis",
abstract = "Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis.",
author = "Joan Lee and Indong Jun and Park, {Hyun Ji} and Kang, {Taek Jin} and Heungsoo Shin and Seung-Woo Cho",
year = "2014",
month = "1",
day = "13",
doi = "10.1021/bm401605f",
language = "English",
volume = "15",
pages = "361--372",
journal = "Biomacromolecules",
issn = "1525-7797",
publisher = "American Chemical Society",
number = "1",

}

Lee, J, Jun, I, Park, HJ, Kang, TJ, Shin, H & Cho, S-W 2014, 'Genetically engineered myoblast sheet for therapeutic angiogenesis', Biomacromolecules, vol. 15, no. 1, pp. 361-372. https://doi.org/10.1021/bm401605f

Genetically engineered myoblast sheet for therapeutic angiogenesis. / Lee, Joan; Jun, Indong; Park, Hyun Ji; Kang, Taek Jin; Shin, Heungsoo; Cho, Seung-Woo.

In: Biomacromolecules, Vol. 15, No. 1, 13.01.2014, p. 361-372.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetically engineered myoblast sheet for therapeutic angiogenesis

AU - Lee, Joan

AU - Jun, Indong

AU - Park, Hyun Ji

AU - Kang, Taek Jin

AU - Shin, Heungsoo

AU - Cho, Seung-Woo

PY - 2014/1/13

Y1 - 2014/1/13

N2 - Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis.

AB - Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84892623578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892623578&partnerID=8YFLogxK

U2 - 10.1021/bm401605f

DO - 10.1021/bm401605f

M3 - Article

C2 - 24304175

AN - SCOPUS:84892623578

VL - 15

SP - 361

EP - 372

JO - Biomacromolecules

JF - Biomacromolecules

SN - 1525-7797

IS - 1

ER -