Liposome-Mediated MicroRNA Delivery: An Additional Layer of Gene Network Regulation and Nuclear Reprogramming.

BACKGROUND: Developing miRNA-mediated cell engineering introduces a novel technology for cell reprogramming and generating patient-specific tissues for therapeutic use, facilitating basic research on human adult stem cells. Furthermore, optimizing a reprogramming method without transduction minimizes the risk of tumorigenesis, especially for reprogrammed cells. This study aimed to explore the use of liposomes as vehicles for delivering miRNAs to cells, focusing on their role in regulating gene networks and facilitating nuclear reprogramming. METHODS: This study utilized cationic liposomal nanoparticles preserved under different conditions to introduce miRNAs into hMSCs. Using qPCR, the effective induction of pluripotency factors (OCT4, SOX2, and NANOG) was examined. RESULTS: Results indicated that miR-302a and miR-34a regulate pluripotency by interacting with key transcription factors, including OCT4, SOX2, and NANOG. Notably, the expression pattern of OCT4 showed that lipoplexes containing miR-302a increased the expression of this gene, while in the case of miR-34a, it decreased. Additionally, the study found that pluripotency precursors can be induced by delivering liposomal microRNA (LP-miRs). CONCLUSION: LP-miRs, as small-molecule therapeutics, can influence reprogramming/engineering and the conversion of cells into other lineages. These findings have significant implications for our understanding of the mechanisms underlying the regulation of pluripotency and may have potential applications in regenerative medicine.