Theranostics 2019; 9(8):2325-2345. doi:10.7150/thno.30030

Research Paper

Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice

Javier Abello1,2, Tuyen Duong Thanh Nguyen3,4, Ramesh Marasini3,4, Santosh Aryal3,4✉, Mark Louis Weiss1,5✉

1. Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA
2. Department of Food, Nutrition, Dietetics and Health, Kansas State University, Manhattan, KS 66506, USA
3. Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA
4. Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA
5. Midwest Institute of Comparative Stem Cell Biology, Kansas State University, Manhattan, KS 66506, USA

Abstract

We speculate that exosomes derived from human umbilical cord mesenchymal stromal cells (HUC-MSCs) will accumulate within tumors and have the potential for both tumor location or drug delivery.

Methods: To determine proof of concept, HUC-MSC exosomes were labeled with an MRI contrast agent, gadolinium, or a near infrared dye. Exosome accumulation within ectopic osteosarcoma tumor-bearing mice was determined by 14.1 T MRI or bioimaging over 24-48 h after injection. In vitro studies examine the accumulation and physiological effect of exosomes on human and mouse osteosarcoma cell lines by MTT assay, confocal microscopy, and flow cytometry.

Results: Systemic HUC-MSC exosomes accumulated continuously in tumor over a 24-48 h post-injection period. In contrast, synthetic lipid nanoparticles accumulate in tumor only for the first 3 h post-injection.

Conclusion: These results suggest that HUC-MSCs exosomes accumulate within human or mouse osteosarcoma cells in vitro and in vivo over a 24 to 48 h after infusion.

Keywords: Extracellular vesicles, non-invasive imaging, ectopic osteosarcoma model, gadolinium nanoparticle.

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How to cite this article:
Abello J, Nguyen TDT, Marasini R, Aryal S, Weiss ML. Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice. Theranostics 2019; 9(8):2325-2345. doi:10.7150/thno.30030. Available from http://www.thno.org/v09p2325.htm