Engineered IGF-1-expressing adipose-derived stem cell sheet fragments promote urethral sphincter tissue regeneration

Stem cell implantation is a promising tissue regeneration strategy. However, the hypoxic and nutrient-poor microenvironment of damaged tissue sites limit stem cell viability and engraftment. Thus, in vitro generated stem cell sheets are being developed as a promising strategy for overcoming the limitations of free stem cell implantation. Here, adipose-derived stem cells (ADSCs) transfected with synthetic, chemically modified mRNA (modRNA) encoding insulin-like growth factor-1 (modIGF-1) improve the function of ADSCs. A magnetic force tissue engineering technology (Mag-TE) is used to generate sheets of magnetite-nanoparticle-labeled modIGF-1 transfected ADSCs (MNP-labeled ADSCs modIGF-1 ) more rapidly than conventional cell sheet assembly techniques. The injection of MNP-labeled ADSC modIGF-1 sheet fragments into a rat model of stress urinary incontinence (SUI) improves urethral sphincter function by promoting neovascularization and muscle tissue regeneration. These findings suggest that the genetically engineered stem cell sheet fragments generated using a combination of Mag-TE and modRNA technologies represent a promising novel treatment strategy for SUI.