Differentialin vivobiodistribution of131I-labeled exosomes from diverse cellular origins and its implication in the theranostic application
Authors: Rashid Mohammad H. , Borin Thaiz F. , Ara Roxan , Angara Kartik , Cai Jingwen , Achyut Bhagelu R. , Liu Yutao , Arbab Ali S. 
Published: March 2019

Exosomes are critical mediators of intercellular crosstalk and regulator of cellular/tumor microenvironment. Exosomes have great prospects for clinical application as theranostic and prognostic probe. Nevertheless, the advancement of the exosomes research has been thwarted by limited knowledge elucidating the most efficient isolation method and theirin vivotrafficking. Here we have showed that combination of two size-based methods using 0.20 µm syringe filter and 100k centrifuge membrane filter followed by ultracentrifugation method yields a greater number of uniform exosomes. We also demonstrated the visual representation and quantification of differentialin vivodistribution of radioisotope131I-labelled exosomes from diverse cellular origins, e.g., tumor cells with or without treatments (HET0016 and GW2580), myeloid-derived suppressor cells and endothelial progenitor cells. We also determined that the distribution was dependent on the protein/cytokine contents of the exosomes. The appliedin vivoimaging modalities can be utilized to monitor disease progression, metastasis, and exosome-based targeted therapy.

Abbreviations

bFGF

basic fibroblast growth factor

CSF1R

colony stimulating factor 1 receptor

CT

computed tomography

CTLA4

cytotoxic T-lymphocyte-associated protein 4

EGF

epidermal growth factor

EMT

epithelial to mesenchymal transition

EVs

extracellular vesicles

EPCs

endothelial progenitor cells

FasL

Fas ligand

G-CSF

granulocyte-colony stimulating factor

GM-CSF

granulocyte-macrophage colony-stimulating factor

HGF

hepatocyte growth factor

HSP

heat shock protein

ICAM-1

intercellular adhesion molecule 1

IFN-gamma

interferon gamma

IL – 1beta

interleukin-1 beta

IL – 1ra

interleukin-1 receptor antagonist

IL – 2

interleukin-2

IL – 4

interleukin-4

IL – 6

interleukin-6

IL – 7

interleukin-7

IL – 10

interleukin-10

IL – 12

interleukin-12

IL – 13

interleukin-13

IL – 17

interleukin-17

KC

keratinocyte-derived chemokine

LIX

lipopolysaccharide-induced CXC chemokine

M-CSF

macrophage colony-stimulating factor

MCP-1

monocyte chemoattractant protein 1

MDC

macrophage-derived chemokine

MDSCs

myeloid derived suppressor cells

MFP

mammary fat pad

MIP-1α

macrophage-inflammatory protein-1alpha

MMP-2

matrix metalloproteinase-2

MRI

magnetic resonance imaging

NIS

sodium iodide symporter

NTA

nanoparticle tracking analysis

PET

positron emission tomography

PF-4

platelet factor 4

RANTES

regulated on activation, normal T cell expressed and secreted

ROIs

region of interest

SDF-1α

stromal cell-derived factor-1

SEM

standard error of the mean

SPECT

single-photon emission computed tomography

SCF

stem cell factor

TAMs

tumor-associated macrophages

TEM

transmission electron microscopy

TIMP 2

tissue inhibitors of metalloproteinases 2

TLPC

thin layer paper chromatography

TME

tumor microenvironment

TNF-α

tumor necrosis factor-α

TSLP

thymic stromal lymphopoietin

UC

ultracentrifugation

VEGF-A

vascular endothelial growth factor A

VEGFR2

vascular endothelial growth factor receptor 2.