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.

Graphical Abstract

Keywords:

• magnetic fluorescent nanoparticle
• induced pluripotent stem cell
• trabecular meshwork
• in vivo monitoring
• specific targeting

Abbreviations

TM, trabecular meshwork; NP, nanoparticle; iPSC, induced pluripotent stem cell; PLGA, polylactic acid-glycolic acid; SPIO, superparamagnetic iron oxide; PSC, PLGA-SPIO-Cypate; NIR, near-infrared imaging; miPSC-TM, mouse iPSC-derived TM; IOP, intraocular pressure; AH, aqueous humor; MSC, mesenchymal stem cell; MRI, magnetic resonance imaging; IHC staining, immunocytochemical staining; WB, Western blot; DEX, dexamethasone; CLAN, cross-linked actin network.

Acknowledgments

We thank Prof. Budd A. Tucker at the University of Iowa for providing mouse iPSCs and Dr. Xuejiao Yang (Affiliated Hospital of Qingdao University, Qingdao, China) for giving immortalized human TM cells. This study was supported by National Key Research and Development Program 2018YFA0109500, National Natural Science Foundation of China 81870653, Shandong Key Research and Development Program 2019GSF107075, and Taishan Scholar Youth Expert Program tsqn202103055.

Disclosure

Qilong Cao is affiliated with Qingdao Haier Biotech Co. Ltd. The authors report no other conflicts of interest in this work.