A novel gene delivery approach using metal organic frameworks in human islet-derived progenitor cells

The ability to regenerate insulin-producing β cells is the ultimate goal for treatment of type 1 diabetes. Several sources of stem cells have been investigated by studying their differential potential to form insulin-producing β cells that can be used for replacement therapy. Progenitor cells derived from human islets that are lineage committed have been shown to be better alternatives with regard to their differentiation capabilities for the generation of insulin-producing β-like cells. Controlling the differentiation of progenitor cells is a vital approach in exploiting cellular expansion, mesenchymal transition and β-cell generation. One of the most powerful and useful methods involve the intracellular delivery of biomolecules like genes, miRNAs, siRNAs, proteins, and peptides. However, the delivery vehicle used for such approaches is the most significant factor that determines the in vivo efficacy. Current delivery systems, although promising, are deterred by issues like toxicity, sustained release, loading capacity, and cost-effectiveness. In this chapter, we show an alternative nanomaterial called metal organic frameworks (MOFs) as gene delivery systems in human islet-derived progenitor cells (hIPCs). Based on our results, we believe that nanoscale MOFs can function as controlled cellular delivery agents that deliver, protect, and maintain functional activity of genes or other bioactive molecules into the cytoplasm or nucleus of progenitor cells. Here, we describe the details for the synthesis, characterization, and transfection of selected, biocompatible MOFs in hIPCs.