Peptide-mediated intracellular delivery of miRNA-29b for osteogenic stem cell differentiation

Biomaterials. 2013 Jun;34(17):4347-59. doi: 10.1016/j.biomaterials.2013.02.039. Epub 2013 Mar 9.

Abstract

Stem cell differentiation is modulated by several key molecules, including cytokines, hormones, and engineered peptides. Emerging evidence suggests that microRNA has potential applications in stem cell engineering, such as in osteoblastic differentiation. MicroRNAs (miRNAs) bind to the 3'-untranslated region (UTR) sequence of target mRNA, thereby attenuating protein synthesis. Our goal was to evaluate the delivery of miRNA, i.e., miRNA-29b, to stem cells to promote osteoblastic differentiation because this miRNA is known to target anti-osteogenic factors gene expression. Despite the important role of miRNAs, their application has been limited due to poor cell/tissue penetration. The authors attempted to overcome this limitation by using a cell-penetrating peptide (CPP) carrier. Herein, the arginine-rich CPP, called the lowmolecular weight protamine (LMWP), is the sequence from natural protamine. We worked out the difficult problem to transfect into hMSCs by the complex with LMWP, and then we investigated synthetic double-stranded miR-29b could be induced osteoblast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biophysical Phenomena / drug effects
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Survival / drug effects
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / pharmacology*
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Gene Transfer Techniques*
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Particle Size
  • Protamines / chemistry
  • Static Electricity

Substances

  • Cell-Penetrating Peptides
  • MIRN29a microRNA, human
  • MicroRNAs
  • Protamines