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

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2022 Mar 29

PMID 35345785

Authors

Xiangji Wang

Qilong Cao

Shen Wu

Mohammad Reza Bahrani Fard

Ningli Wang

Jie Cao

Wei Zhu

Affiliations

Soon will be listed here.

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.

Citing Articles

iPSC-derived cells stimulate ABCG2/NES endogenous trabecular meshwork cell proliferation and tissue regeneration.

Xi G, Feng P, Zhang X, Wu S, Zhang J, Wang X Cell Prolif. 2024; 57(7):e13611.

PMID: 38356373 PMC: 11216930. DOI: 10.1111/cpr.13611.

Nanotechnology in Retinal Disease: Current Concepts and Future Directions.

Mehta N, Mehta S J Ocul Pharmacol Ther. 2023; 40(1):3-12.

PMID: 38052063 PMC: 10890960. DOI: 10.1089/jop.2023.0083.

iPSCs-Based Therapy for Trabecular Meshwork.

Zhu W, Zhang X, Wu S, Wang N, Kuehn M Handb Exp Pharmacol. 2023; 281:277-300.

PMID: 37495850 DOI: 10.1007/164_2023_671.

Improved magnetic delivery of cells to the trabecular meshwork in mice.

Fard M, Chan J, Sanchez Rodriguez G, Yonk M, Kuturu S, Read A Exp Eye Res. 2023; 234:109602.

PMID: 37488007 PMC: 10530071. DOI: 10.1016/j.exer.2023.109602.

A bibliometric analysis of the application of stem cells in glaucoma research from 1999 to 2022.

Tao Y, Zhang Q, Meng M, Huang J Front Cell Dev Biol. 2023; 11:1081898.

PMID: 36743419 PMC: 9889543. DOI: 10.3389/fcell.2023.1081898.

References

Veiseh O, Gunn J, Zhang M . Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev. 2009; 62(3):284-304. PMC: 2827645. DOI: 10.1016/j.addr.2009.11.002. View

Momeni A, Neelamegham S, Parashurama N . Current challenges for the targeted delivery and molecular imaging of stem cells in animal models. Bioengineered. 2016; 8(4):316-324. PMC: 5553333. DOI: 10.1080/21655979.2016.1233090. View

Yu Z, Li Q, Wang J, Yu Y, Wang Y, Zhou Q . Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field. Nanoscale Res Lett. 2020; 15(1):115. PMC: 7239959. DOI: 10.1186/s11671-020-03344-7. View

Zhang L, Xue H, Gao C, Carr L, Wang J, Chu B . Imaging and cell targeting characteristics of magnetic nanoparticles modified by a functionalizable zwitterionic polymer with adhesive 3,4-dihydroxyphenyl-l-alanine linkages. Biomaterials. 2010; 31(25):6582-8. DOI: 10.1016/j.biomaterials.2010.05.018. View

Petters C, Irrsack E, Koch M, Dringen R . Uptake and metabolism of iron oxide nanoparticles in brain cells. Neurochem Res. 2014; 39(9):1648-60. DOI: 10.1007/s11064-014-1380-5. View

Schuman J, Hee M, Arya A, Puliafito C, Fujimoto J, Swanson E . Optical coherence tomography: a new tool for glaucoma diagnosis. Curr Opin Ophthalmol. 1995; 6(2):89-95. DOI: 10.1097/00055735-199504000-00014. View

Ding Q, Zhu W, Cook A, Anfinson K, Tucker B, Kuehn M . Induction of trabecular meshwork cells from induced pluripotent stem cells. Invest Ophthalmol Vis Sci. 2014; 55(11):7065-72. PMC: 4224582. DOI: 10.1167/iovs.14-14800. View

Farrell E, Wielopolski P, Pavljasevic P, van Tiel S, Jahr H, Verhaar J . Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo. Biochem Biophys Res Commun. 2008; 369(4):1076-81. DOI: 10.1016/j.bbrc.2008.02.159. View

Goodfellow F, Simchick G, Mortensen L, Stice S, Zhao Q . Tracking and Quantification of Magnetically Labeled Stem Cells using Magnetic Resonance Imaging. Adv Funct Mater. 2017; 26(22):3899-3915. PMC: 5526633. DOI: 10.1002/adfm.201504444. View

10.

Naldini L, Blomer U, Gage F, Trono D, Verma I . Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci U S A. 1996; 93(21):11382-8. PMC: 38066. DOI: 10.1073/pnas.93.21.11382. View

11.

Yun H, Zhou Y, Wills A, Du Y . Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure. J Ocul Pharmacol Ther. 2016; 32(5):253-60. PMC: 4904164. DOI: 10.1089/jop.2016.0005. View

12.

Cao J, Chen D, Huang S, Deng D, Tang L, Gu Y . Multifunctional near-infrared light-triggered biodegradable micelles for chemo- and photo-thermal combination therapy. Oncotarget. 2016; 7(50):82170-82184. PMC: 5347683. DOI: 10.18632/oncotarget.10320. View

13.

Schafer R, Kehlbach R, Muller M, Bantleon R, Kluba T, Ayturan M . Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability. Cytotherapy. 2009; 11(1):68-78. DOI: 10.1080/14653240802666043. View

14.

Fu Y, Kraitchman D . Stem cell labeling for noninvasive delivery and tracking in cardiovascular regenerative therapy. Expert Rev Cardiovasc Ther. 2010; 8(8):1149-60. PMC: 3096938. DOI: 10.1586/erc.10.106. View

15.

Manuguerra-Gagne R, Boulos P, Ammar A, Leblond F, Krosl G, Pichette V . Transplantation of mesenchymal stem cells promotes tissue regeneration in a glaucoma model through laser-induced paracrine factor secretion and progenitor cell recruitment. Stem Cells. 2013; 31(6):1136-48. DOI: 10.1002/stem.1364. View

16.

Kaneko Y, Ohta M, Inoue T, Mizuno K, Isobe T, Tanabe S . Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells. Sci Rep. 2016; 6:19640. PMC: 4725980. DOI: 10.1038/srep19640. View

17.

Huang A, Mohindroo C, Weinreb R . Aqueous Humor Outflow Structure and Function Imaging At the Bench and Bedside: A Review. J Clin Exp Ophthalmol. 2016; 7(4). PMC: 5079182. DOI: 10.4172/2155-9570.1000578. View

18.

Bulte J . Superparamagnetic iron oxides as MPI tracers: A primer and review of early applications. Adv Drug Deliv Rev. 2018; 138:293-301. PMC: 6449195. DOI: 10.1016/j.addr.2018.12.007. View

19.

Page M, Lourenco A, David T, LeBeau A, Cattaruzza F, Castro H . Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography. Nat Commun. 2015; 6:8448. PMC: 4593073. DOI: 10.1038/ncomms9448. View

20.

Han Z, Lv L, Ma Y, Wang Z, Liu Y, Zhang M . Cypate-mediated thermosensitive nanoliposome for tumor imaging and photothermal triggered drug release. J Biophotonics. 2017; 10(12):1607-1616. DOI: 10.1002/jbio.201600270. View