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

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.