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Biodistribution of poly clustered superparamagnetic iron oxide nanoparticle labeled mesenchymal stem cells in aminoglycoside induced ototoxic mouse model

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Abstract

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC’s were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery.

Graphic abstract

The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC’s to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy.

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Abbreviations

PCS nanoparticle:

Poly clustered superparamagnetic iron oxide nanoparticles

PLGA:

Poly lactic-co-glycolic acid

Cy5.5:

Cyanine 5.5

MSC:

Mesenchymal stem cell

SDF-1:

Stromal cell derived factor 1

CXCR4:

Chemokine receptor type 4

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Acknowledgements

This work was supported by the Technology Innovation Program (20010587, Development and Dissemination on National Standard Reference Data) funded By the Ministry of Trade, Industry & Energy (MOTIE, Korea) and by National Information Society Agency (NIA) funded by the Ministry of Science, ICT.

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Authors and Affiliations

  1. Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, 26426, South Korea

    Ye Ji Ahn, Jin Sil Choi, Su Hoon Lee, Dong Jun Park, Jeong Eun Park & Young Joon Seo

  2. Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do, 26426, South Korea

    Ye Ji Ahn, Jin Sil Choi, Su Hoon Lee, Dong Jun Park, Jeong Eun Park & Young Joon Seo

  3. Department of Biomedical Engineering, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwon- do, 26493, South Korea

    Wan Su Yun, Woo Cheol Kim & Jaehong Key

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  1. Ye Ji Ahn
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Contributions

YJA and WSY: equally contributed in conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; JSC: data analysis and interpretation; WCK: assembly of data, data analysis and interpretation; SHL: collection and assembly of data, data analysis and interpretation; DJP: data analysis and interpretation; JEP: collection and assembly of data, data analysis and interpretation; JK: conception and design, administrative support, data analysis and interpretation, final approval of manuscript; YJS: administrative support, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.

Corresponding authors

Correspondence to Jaehong Key or Young Joon Seo.

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Conflict of interest

Author Ahn, Yeji declares that she has no conflict of interest. Author Yoon, Wan Su declares that he has no conflict of interest. Author Choi, Jin Sil declares that she has no conflict of interest. Author Kim, Woo Cheol declares that he has no conflict of interest. Author Lee, Su Hoon declares that he has no conflict of interest. Author Park, Dong Jun declares that he has no conflict of interest. Author Park, Jeong Eun declares that she has no conflict of interest. Author Key, Jaehong declares that he has no conflict of interest. Author Seo, Young Joon declares that he has no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Ahn, Y.J., Yun, W.S., Choi, J.S. et al. Biodistribution of poly clustered superparamagnetic iron oxide nanoparticle labeled mesenchymal stem cells in aminoglycoside induced ototoxic mouse model. Biomed. Eng. Lett. 11, 39–53 (2021). https://doi.org/10.1007/s13534-020-00181-6

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  • DOI: https://doi.org/10.1007/s13534-020-00181-6

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