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

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.

Integration of gadolinium in nanostructure for contrast enhanced‐magnetic resonance imaging

“…Various polymer-based nanocarriers (polymeric micelles, nano-hydrogels, polymeric particles [nanosphere and nanocapsule], polymersomes, dendrimers, etc.) have been reported for the integration of gadolinium chelates as nanoscale CAs for MR imaging (Abello, Thanh Nguyen, Marasini, Aryal, & Weiss, 2019;Aryal et al, 2013;Aryal et al, 2014;Debroye & Parac-Vogt, 2014;Gizzatov et al, 2014;Heffern et al, 2014;Mi et al, 2015;Zhang et al, 2018). Due to their superior advantages in improving water solubility, decreasing toxicity, higher biodegradability, enhanced circulation half-lives, and ease of F I G U R E 7 (a) and (b) are the schematic illustration of the synthetic strategies for the Gd 3+ loaded MSNs by surface conjugation and entrapment inside core, respectively, (c) graphical representation of the synthesis of MSN-dendron-Gd (nanoprobe), (d) study of r 1 obtained from the slopes of linear fits of experimental data against Gd 3+ concentration used in aqueous condition where blue represents nanoprobe and back for DTPA-Gd phantom study at 0.5 T and E) in vivo T 1 image of mice after injection of nanoprobe and its corresponding quantitative data.…”

Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine

“…In this study, they found that GdL-EXs mainly accumulated in the liver (38%), tumor (18%) and kidney (8%) at 24 h after intravenous injection, and DiR-EXs mostly appeared in the liver, spleen, and tumor at 48 h after intravenous administration [94]. DiR-EXs displayed longer circulation times than PEGylated nanoparticles [94]. In another study, Wiklander et al observed a similar distribution where DiR-labeled EVs mainly appeared in the liver and spleen in mouse tissue at 24 h after intravenous injection [95].…”

“…The biodistribution of EVs affects their efficiency in the delivery of therapeutic entities as part of the treatment of various diseases. Abello et al analyzed the biodistribution of EXs by labeling hucMSC-EXs with gadolinium lipid (GdL-EXs) or a near-infrared dye; i.e., 1,1'-dioctadecyl-3,3,3',3'tetramethylindotricarbocyanine iodide (DiR-EXs), in tumor bearing mice [94]. In this study, they found that GdL-EXs mainly accumulated in the liver (38%), tumor (18%) and kidney (8%) at 24 h after intravenous injection, and DiR-EXs mostly appeared in the liver, spleen, and tumor at 48 h after intravenous administration [94].…”

“…They found that MSCs traveled to lung tumors replicated and released both viruses to the tumor microenvironment, displayed enhanced antitumor activity, and prolonged survival of tumor-bearing mice [114]. SC-EVs have more advantages than stem cells and they also display tropism for tumor sites [94]. Tests of their virus-delivery ability is promising in the field of oncotherapy.…”

Enhanced therapeutic effects of MSC-derived extracellular vesicles with an injectable collagen matrix for experimental acute kidney injury treatment

“…Therefore, we introduced the EVs labeled with Gaussia luciferase (Gluc), which is unique to our laboratory, and used molecular imaging to achieve real-time monitoring in vivo. With the ability to visualize and to measure biological processes in intact animals instead of performing histological analysis at discrete time points, molecular imaging holds great potential for the study of EV-based therapies [11,15].…”