Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier

Yujung Chang; Euiyeon Lee; Junyeop Kim; Yoo Wook Kwon; Youngeun Kwon; Jongpil Kim

doi:10.1016/j.biomaterials.2018.11.034

Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier

Yujung Chang, Euiyeon Lee, Junyeop Kim, Yoo Wook Kwon, Youngeun Kwon, Jongpil Kim

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

65 Scopus citations

Abstract

The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.

Original language	English
Pages (from-to)	500-509
Number of pages	10
Journal	Biomaterials
Volume	192
DOIs	https://doi.org/10.1016/j.biomaterials.2018.11.034
State	Published - Feb 2019

Keywords

Cardiac reprogramming
Cardiomyocytes
Gold nanoparticles
Heart regeneration
In vivo reprogramming

UN SDGs

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

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10.1016/j.biomaterials.2018.11.034

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title = "Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier",

abstract = "The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.",

keywords = "Cardiac reprogramming, Cardiomyocytes, Gold nanoparticles, Heart regeneration, In vivo reprogramming",

author = "Yujung Chang and Euiyeon Lee and Junyeop Kim and Kwon, {Yoo Wook} and Youngeun Kwon and Jongpil Kim",

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year = "2019",

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doi = "10.1016/j.biomaterials.2018.11.034",

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AU - Chang, Yujung

AU - Lee, Euiyeon

AU - Kim, Junyeop

AU - Kwon, Yoo Wook

AU - Kwon, Youngeun

AU - Kim, Jongpil

PY - 2019/2

Y1 - 2019/2

N2 - The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.

AB - The reprogramming of induced cardiomyocytes (iCMs) has shown potential in regenerative medicine. However, in vivo reprogramming of iCMs is significantly inefficient, and novel gene delivery systems are required to more efficiently and safely induce in vivo reprogramming of iCMs for therapeutic applications in heart injury. In this study, we show that cationic gold nanoparticles (AuNPs) loaded with Gata4, Mef2c, and Tbx5 function as nanocarriers for cardiac reprogramming. The AuNP/GMT/PEI nanocomplexes show high reprogramming efficiency in human and mouse somatic cells with low cytotoxicity and direct conversion into iCMs without integrating factors into the genome. Importantly, AuNP/GMT/PEI nanocomplexes led to efficient in vivo conversion into cardiomyocytes after myocardial infarction (MI), resulting in the effective recovery of cardiac function and scar area. Taken together, these results show that the AuNP/GMT/PEI nanocarrier can be used to develop effective therapeutics for heart regeneration in cardiac disease patients.

KW - Cardiac reprogramming

KW - Cardiomyocytes

KW - Gold nanoparticles

KW - Heart regeneration

KW - In vivo reprogramming

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DO - 10.1016/j.biomaterials.2018.11.034

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SN - 0142-9612

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SP - 500

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JO - Biomaterials

JF - Biomaterials

ER -

Efficient in vivo direct conversion of fibroblasts into cardiomyocytes using a nanoparticle-based gene carrier

Abstract

Keywords

UN SDGs

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