Chitosan/DNA nanoparticles characteristics determine the transfection efficacy of gene delivery to human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) show enormous potential in regenerative medicine and tissue engineering. However, current use of hMSCs in clinics is still limited because there is no appropriate way to control their behavior in vivo, such as differentiation to a desired cell type. Genetic modification may provide an opportunity to control the cells in an active manner. One of the major hurdles for genetic manipulation of hMSCs is the lack of an efficient and safe gene delivery system. Herein, biocompatible calcium phosphate (CaP)-based nanoparticles stabilized with a catechol-derivatized hyaluronic acid (dopa-HA) conjugate were used as a carrier for gene transfection to hMSCs for improved differentiation. Owing to the specific interactions between HA and CD44 of bone marrow-derived hMSCs, dopa-HA/CaP showed significantly higher transfection in hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxicity. The co-delivery of a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and micro RNA 148b (miRNA-148b) by dopa-HA/CaP achieved significantly improved osteogenic differentiation of hMSCs.

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The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis

Biomaterials ◽

10.1016/j.biomaterials.2010.08.086 ◽

2011 ◽

Vol 32 (1) ◽

pp. 268-278 ◽

Cited By ~ 52

Author(s):

Jae-Hwan Kim ◽

Ji Sun Park ◽

Han Na Yang ◽

Dae Gyun Woo ◽

Su Yeon Jeon ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Gene Delivery ◽

Human Mesenchymal Stem Cells ◽

Plga Nanoparticles ◽

Sox9 Gene

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Efficient delivery of C/EBP beta gene into human mesenchymal stem cells via polyethylenimine-coated gold nanoparticles enhances adipogenic differentiation

Scientific Reports ◽

10.1038/srep33784 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 18

Author(s):

Joydeep Das ◽

Yun-Jung Choi ◽

Hideyo Yasuda ◽

Jae Woong Han ◽

Chankyu Park ◽

...

Keyword(s):

Stem Cells ◽

Gold Nanoparticles ◽

Mesenchymal Stem Cells ◽

Gene Delivery ◽

Gene Transfection ◽

Adipogenic Differentiation ◽

Human Mesenchymal Stem Cells ◽

Luciferase Assay ◽

Beta Gene ◽

Lipofectamine 2000

Abstract The controlled differentiation of stem cells via the delivery of specific genes encoding appropriate differentiation factors may provide useful models for regenerative medicine and aid in developing therapies for human patients. However, the majority of non-viral vectors are not efficient enough to manipulate difficult-to-transfect adult human stem cells in vitro. Herein, we report the first use of 25 kDa branched polyethylenimine-entrapped gold nanoparticles (AuPEINPs) and covalently bound polyethylenimine-gold nanoparticles (AuMUAPEINPs) as carriers for efficient gene delivery into human mesenchymal stem cells (hMSCs). We determined a functional application of these nanoparticles by transfecting hMSCs with the C/EBP beta gene, fused to EGFP, to induce adipogenic differentiation. Transfection efficacy with AuPEINPs and AuMUAPEINPs was 52.3% and 40.7%, respectively, which was 2.48 and 1.93 times higher than that by using Lipofectamine 2000. Luciferase assay results also demonstrated improved gene transfection efficiency of AuPEINPs/AuMUAPEINPs over Lipofectamine 2000 and polyethylenimine. Overexpression of exogenous C/EBP beta significantly enhanced adipogenesis in hMSCs as indicated by both of Oil Red O staining and mRNA expression analyses. Nanoparticle/DNA complexes exhibited favorable cytocompatibility in hMSCs. Taken together, AuPEINPs and AuMUAPEINPs potentially represent safe and highly efficient vehicles for gene delivery to control hMSC differentiation and for therapeutic gene delivery applications.

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