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MicroRNA-mediated non-viral direct conversion of embryonic fibroblasts to cardiomyocytes: comparison of commercial and synthetic non-viral vectors
- Source :
- Journal of biomaterials science. Polymer edition. 28(10-12)
- Publication Year :
- 2017
-
Abstract
- Technological advances opened up new ways of directing cell fate conversion from one cell lineage to another. The direct cell conversion technique has recently attracted much attention in regenerative medicine to treat devastated organs and tissues, particularly having limited regenerative capacity such as the heart and brain. Unfortunately, its clinical application is severely limited due to a safety concern and immunogenicity of viral vectors, as human gene therapy did in the beginning stages. In this study, we examined the possibility of adopting non-viral vectors to direct cell conversion from mouse embryonic fibroblasts to induced cardiomyocytes (iCM) by transient transfection of four types of chemically synthesized micro-RNA mimics (miRNA-1, 133, 208, and 499). Herein, we tested several commercial and synthetic non-viral gene delivery carriers, which could be divided into three different categories: polymers [branched PEI (bPEI), bioreducible PEI (PEI-SS), deoxycholic acid-conjugated PEI (DA-PEI), jetPEI™, SuperFect™], lipids (Lipofectamine 2000™), and peptides (PepMute™). According to the analyses of physicochemical properties, cellular uptake, and cytotoxicity of the carrier/miRNA complexes, DA-PEI exhibited excellent miRNA delivery efficiency to mouse embryonic fibroblasts. One week after a single treatment of DA-PEI/miRNA without other adjuvants, the cells started to express cardiomyocyte-specific markers, such as α-actinin and α-MHC, indicating the formation of cardiomyocyte-like cells. Although the overall frequency of non-viral vector induced cardiomyogenic transdifferentiation was quite low (ca. 0.2%), this study can provide compelling support to develop clinically applicable transdifferentiation techniques.
- Subjects :
- 0301 basic medicine
Polymers
Genetic enhancement
Cell
Biomedical Engineering
Biophysics
Bioengineering
macromolecular substances
Gene delivery
Biology
Cell fate determination
Transfection
Regenerative medicine
Viral vector
Biomaterials
03 medical and health sciences
Mice
medicine
Animals
Myocytes, Cardiac
Drug Carriers
Transdifferentiation
Biological Transport
Fibroblasts
Embryo, Mammalian
Embryonic stem cell
Molecular biology
Lipids
Cell biology
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Peptides
Subjects
Details
- ISSN :
- 15685624
- Volume :
- 28
- Issue :
- 10-12
- Database :
- OpenAIRE
- Journal :
- Journal of biomaterials science. Polymer edition
- Accession number :
- edsair.doi.dedup.....3bafe828fdc0cc6c4a2432d2b8574e87