Gold nanorod delivery of LSD1 siRNA induces human mesenchymal stem cell differentiation

Mater Sci Eng C Mater Biol Appl. 2015 Sep:54:142-9. doi: 10.1016/j.msec.2015.05.013. Epub 2015 May 8.

Abstract

Over the past decade, theranostic nanoparticles with microsize and multifunctional ability have emerged as a new platform in biomedical field, such as cancer therapy, optical imaging and gene therapy. Gene therapy has been recently shown as a promising tool for tissue engineering as safe and effective nanotechnology-based delivery methods are developed. Controlling adhesion and differentiation of stem cells is critical for tissue regeneration. In this study, we have developed poly-sodium 4-styrenesulfonate (PSS) and poly-allylamine hydrochloride (PAH) coated AuNR-based nanocarriers, which are capable of delivering small interfering RNA (siRNA) against LSD1 to induce the differentiation of human mesenchymal stem cells. To further study the mechanism, we tested the stemness and differentiation genes and found that they have been changed with LSD1 down-regulation. In addition, with the hepatocyte growth factor (HGF), LSD1 siRNA delivery by AuNRs could promote the differentiation of the human mesenchymal stem cells (human MSCs) into a hepatocyte lineage in vitro. Our results suggest for the first time use of AuNRs as nanocarriers of delivery LSD1 siRNA to induce the differentiation of human MSCs into a hepatocyte lineage, and envision the potential application of nanotechnology in tissue remodeling (such as liver and bone) in vivo, eventually translating to clinical applications.

Keywords: AuNRs; Hepatocyte growth factor; Human mesenchymal stem cells; LSD1; Nanocarriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Differentiation*
  • Cells, Cultured
  • Coated Materials, Biocompatible / chemistry
  • Down-Regulation
  • Drug Delivery Systems
  • Gene Transfer Techniques
  • Genetic Markers
  • Gold / chemistry*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Nanotubes / chemistry*
  • Polyamines / chemistry
  • Polymers / chemistry
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Sulfonic Acids / chemistry
  • Tissue Engineering / methods

Substances

  • Coated Materials, Biocompatible
  • Genetic Markers
  • HGF protein, human
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Polyamines
  • Polymers
  • RNA, Small Interfering
  • Sulfonic Acids
  • polyallylamine
  • Hepatocyte Growth Factor
  • Gold
  • Histone Demethylases
  • KDM1A protein, human
  • styrenesulfonic acid polymer