Receptor-mediated gene delivery into human mesenchymal stem cells using hyaluronic acid-shielded polyethylenimine/pDNA nanogels.

Abstract

Polyethylenimine (PEI) has been used as a vehicle to deliver genes to cancer cells and somatic cells. In this study, cationic polymers of PEI were shielded with anionic polymers of hyaluronic acid (HA) to safely and effectively deliver genes into human mesenchymal stem cells (hMSCs). HA interacted with CD44 in the plasma membranes of hMSCs to facilitate the internalization of HA-shielded PEI/pDNA complexes. The HA-shielded PEI/pDNA nanogels were confirmed by size changes, ζ-potential, and gel retardation assays. HA-shielded nanogels were easily internalized by hMSCs, and this was reduced by pretreatment with a specific monoclonal antibody that blocked CD44. By shielding PEI/pDNA complexes with HA, nanogels were easily internalized to hMSCs when it did not blocked by anti-CD44. These shielded nanogels were also easily internalized by HeLa cells, and this was reduced by pretreatment with an anti-CD44 monoclonal antibody. Following internalization of the SOX9 gene, chondrogenesis of hMSCs was increased, as determined by RT-PCR, real-time quantitative PCR, and histological analyses.

• Authors: Ji Sun Park, Se Won Yi, Hye Jin Kim, Keun-Hong Park
• Journal: Carbohydrate polymers (Carbohydr Polym) Vol. 136 Pg. 791-802 (Jan 20 2016) ISSN: 1879-1344 [Electronic] England
• PMID: 26572414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• DNA, Recombinant
• Gels
• Hyaluronan Receptors
• SOX9 Transcription Factor
• SOX9 protein, human
• Polyethyleneimine
• Hyaluronic Acid

Topics

• Cell Differentiation
• Cells, Cultured
• DNA, Recombinant (administration & dosage, adverse effects)
• Gels (chemistry, pharmacology)
• Genetic Therapy (methods)
• HeLa Cells
• Humans
• Hyaluronan Receptors (metabolism)
• Hyaluronic Acid (chemistry, pharmacology)
• Male
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Plasmids (administration & dosage, adverse effects)
• Polyethyleneimine (chemistry)
• Protein Binding
• SOX9 Transcription Factor (genetics, metabolism)
• Young Adult