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

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 appli...

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Veröffentlicht in:Biomaterials Jg. 192; S. 500 - 509
Hauptverfasser: Chang, Yujung, Lee, Euiyeon, Kim, Junyeop, Kwon, Yoo-Wook, Kwon, Youngeun, Kim, Jongpil
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier Ltd 01.02.2019
Schlagworte:
Animals
cardiac output
Cardiac reprogramming
Cardiomyocytes
Cell Line
Cellular Reprogramming
Cellular Reprogramming Techniques - methods
cytotoxicity
fibroblasts
Fibroblasts - cytology
GATA transcription factors
gene transfer
Gene Transfer Techniques
genes
Gold - chemistry
Gold nanoparticles
Heart regeneration
humans
In vivo reprogramming
Metal Nanoparticles - chemistry
Mice
Mice, Inbred C57BL
myocardial infarction
Myocytes, Cardiac - cytology
nanocarriers
nanogold
patients
somatic cells
Cardiac reprogramming
In vivo reprogramming
Heart regeneration
Cardiomyocytes
Gold nanoparticles
ISSN:0142-9612, 1878-5905, 1878-5905
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2018.11.034