Nanodiamond-based MicroRNA Delivery System Promotes Pluripotent Stem Cells toward Myocardiogenic Reprogramming.

BACKGROUND Gene therapy is the advance therapeutics for supplying or replaceing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. METHODS Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided an crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. RESULTS Here, we applied nanodiamond (ND) as a gene delvery vehicle to carry microRNA (miR-181a), and then tranfected into iPS to promote cardiomyocyte-lineage differentiation. Notably. MiR-181a plays a key role in iPS-dervied cardiomyocyte differentiation which directly target Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. CONCLUSION Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.

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