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

• Published in: Biomaterials 2013-06, Vol.34 (17), p.4347-4359
• Main Authors: Suh, Jin Sook, Lee, Jue Yeon, Choi, Young Suk, Chong, Pyoung Chung, Park, Yoon Jeong
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Amino Acid Sequence; Biophysical Phenomena - drug effects; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Survival - drug effects; Cell-penetrating peptide; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - pharmacology; Dentistry; Flow Cytometry; Gene Expression Regulation - drug effects; Gene Transfer Techniques; Human mesenchymal stem cells; Humans; Intracellular Space - drug effects; Intracellular Space - metabolism; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; MicroRNA-29b; MicroRNAs - metabolism; Molecular Sequence Data; Non-toxic intracellular transfection; Osteoblasts - cytology; Osteoblasts - metabolism; Osteogenesis - drug effects; Osteogenesis - genetics; Osteogenic differentiation; Particle Size; Protamines - chemistry; Static Electricity
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.02.039

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.