Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model

Subin Jung; Jung Hyun Kim; Changwhi Yim; Minhyung Lee; Hyo Jin Kang; Donghoon Choi

doi:10.3892/mmr.2018.9561

Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model

Subin Jung, Jung Hyun Kim, Changwhi Yim, Minhyung Lee, Hyo Jin Kang, Donghoon Choi

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

The present study was conducted in order to improve gene expression efficiency of insulin-like growth factor-1 (IGF-1)-transfected mesenchymal stem cells (MSCs) using a non-viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC-based IGF-1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF-1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene-expressing MSCs was 95.1% by fluorescence-activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF-1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF-1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell-based gene therapy.

Original language	English
Pages (from-to)	5563-5571
Number of pages	9
Journal	Molecular Medicine Reports
Volume	18
Issue number	6
DOIs	https://doi.org/10.3892/mmr.2018.9561
Publication status	Published - 2018 Dec

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea).

Funding Information:
This study was supported by grants from the Korea Health Technology RandD Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea)

Publisher Copyright:
© 2018 Spandidos Publications. All rights reserved.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Genetics
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3892/mmr.2018.9561

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title = "Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model",

abstract = "The present study was conducted in order to improve gene expression efficiency of insulin-like growth factor-1 (IGF-1)-transfected mesenchymal stem cells (MSCs) using a non-viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC-based IGF-1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF-1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene-expressing MSCs was 95.1% by fluorescence-activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF-1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF-1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell-based gene therapy.",

author = "Subin Jung and Kim, {Jung Hyun} and Changwhi Yim and Minhyung Lee and Kang, {Hyo Jin} and Donghoon Choi",

note = "Funding Information: This study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea). Funding Information: This study was supported by grants from the Korea Health Technology RandD Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea) Publisher Copyright: {\textcopyright} 2018 Spandidos Publications. All rights reserved.",

year = "2018",

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doi = "10.3892/mmr.2018.9561",

language = "English",

volume = "18",

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Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model. / Jung, Subin; Kim, Jung Hyun; Yim, Changwhi et al.
In: Molecular Medicine Reports, Vol. 18, No. 6, 12.2018, p. 5563-5571.

Research output: Contribution to journal › Article › peer-review

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AU - Jung, Subin

AU - Kim, Jung Hyun

AU - Yim, Changwhi

AU - Lee, Minhyung

AU - Kang, Hyo Jin

AU - Choi, Donghoon

N1 - Funding Information: This study was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea). Funding Information: This study was supported by grants from the Korea Health Technology RandD Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant nos. HI17C0882 and HI16C2211); the Mid-Career Researcher Program through a National Research Foundation grant funded by the Ministry of Education, Science, and Technology, Republic of Korea (grant no. 2015R1A2A2A01002731); and the Cardiovascular Research Center (Seoul, Korea) Publisher Copyright: © 2018 Spandidos Publications. All rights reserved.

PY - 2018/12

Y1 - 2018/12

N2 - The present study was conducted in order to improve gene expression efficiency of insulin-like growth factor-1 (IGF-1)-transfected mesenchymal stem cells (MSCs) using a non-viral carrier and a simplified method of dual gene selection. The therapeutic efficacy of this MSC-based IGF-1/enhanced green fluorescent protein (EGFP) dual gene sorting system was evaluated in a rat myocardial infarction (MI) model. IGF-1 and EGFP genes were expressed in MSCs in vitro. The purity of dual gene-expressing MSCs was 95.1% by fluorescence-activated cell sorting. Transfected MSCs injected into rats were identified based on green fluorescence, with an increased signal intensity observed in rats injected with sorted cells, compared with unsorted cells. IGF-1 expression levels were additionally increased in the sorted group, and decreases in infarct size, fibrotic area and fraction of apoptotic cells were observed. These results demonstrated that IGF-1 overexpression protects against fibrosis and apoptosis in the myocardium and reduces infarct size following MI. Additionally, the present vector sorting system may potentially be applied to other types of stem cell-based gene therapy.

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Therapeutic effects of a mesenchymal stem cell-based insulin-like growth factor-1/enhanced green fluorescent protein dual gene sorting system in a myocardial infarction rat model

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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