Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair

• DOI: 10.3389/fcell.2023.1127594
• Publication Date: 2023-02-08T06:12:38Z
• Authors: Chun-Chieh Huang; Miya Kang; Kasey Leung; Yu Lu; Sajjad Shirazi; Praveen Gajendrar...; Sriram Ravindran
• Keywords: Extracellular vesicles; Regenerative Medicine

Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, with consistent functionality target specificity are required to achieve the goals of precision medicine tissue engineering. Prior research has identified that miRNA composition mesenchymal contributes significantly towards functionality. In this study, we hypothesized vesicle can be rendered pathway-specific using miRNA-based engineering approach. To test hypothesis, utilized bone repair as model system BMP2 signaling cascade targeted pathway. We engineered increased levels miR-424, potentiator cascade. evaluated physical functional characteristics these their enhanced ability trigger osteogenic differentiation naïve in vitro facilitate vivo. Results indicated retained endocytic demonstrated osteoinductive function by activating SMAD1/5/8 phosphorylation Furthermore, inherent properties remained unaltered. These results serve proof-of-concept for approaches regenerative applications.