Magnetic Nano-Platform Enhanced iPSC-Derived Trabecular Meshwork Delivery and Tracking Efficiency

Abstract

Purpose: Transplantation of stem cells to remodel the trabecular meshwork (TM) has become a new option for restoring aqueous humor dynamics and intraocular pressure homeostasis in glaucoma. In this study, we aimed to design a nanoparticle to label induced pluripotent stem cell (iPSC)-derived TM and improve the delivery accuracy and in vivo tracking efficiency. Methods: PLGA-SPIO-Cypate (PSC) NPs were designed with polylactic acid-glycolic acid (PLGA) polymers as the backbone, superparamagnetic iron oxide (SPIO) nanoparticles, and near-infrared (NIR) dye cypate. In vitro assessment of cytotoxicity, iron content after NPs labeling, and the dual-model monitor was performed on mouse iPSC-derived TM (miPSC-TM) cells, as well as immortalized and primary human TM cells. Cell function after labeling, the delivery accuracy, in vivo tracking efficiency, and its effect on lowering IOP were evaluated following miPSC-TM transplantation in mice. Results: Initial in vitro experiments showed that a single-time nanoparticles incubation was sufficient to label iPSC-derived TM and was not related to any change in both cell viability and fate. Subsequent in vivo evaluation revealed that the use of this nanoparticle not only improves the delivery accuracy of the transplanted cells in live animals but also benefits the dual-model tracking in the long term. More importantly, the use of the magnet triggers a temporary enhancement in the effectiveness of cell-based therapy in alleviating the pathologies associated with glaucoma. Conclusion: This study provided a promising approach for enhancing both the delivery and in vivo tracking efficiency of the transplanted cells, which facilitates the clinical translation of stem cell-based therapy for glaucoma.