Adipose-Derived Mesenchymal Stem Cell Exosomes Suppress Hepatocellular Carcinoma Growth in a Rat Model: Apparent Diffusion Coefficient, Natural Killer T-Cell Responses, and Histopathological Features

Sheung Fat Ko*, Hon Kan Yip, Yen Yi Zhen, Chen Chang Lee, Chia Chang Lee, Chung Cheng Huang, Shu Hang Ng, Jui Wei Lin

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

135 Scopus citations

Abstract

We sought to evaluate the effects of adipose-derived mesenchymal stem cells (ADMSCs) exosomes on hepatocellular carcinoma (HCC) in rats using apparent diffusion coefficient (ADC), natural killer T-cell (NKT-cell) responses, and histopathological features. ADMSC-derived exosomes appeared as nanoparticles (30-90 nm) on electron microscopy and were positive for CD63, tumor susceptibility gene-101, and β-catenin on western blotting. The control (n=8) and exosome-treated (n=8) rats with N1S1-induced HCC underwent baseline and posttreatment day 10 and day 20 magnetic resonance imaging and measurement of ADC. Magnetic resonance imaging showed rapidly enlarged HCCs with low ADCs in the controls. The exosome-treated rats showed partial but nonsignificant tumor reduction, and significant ADC and ADC ratio increases on day 10. On day 20, the exosome-treated rats harbored significantly smaller tumors and volume ratios, higher ADC and ADC ratios, more circulating and intratumoral NKT-cells, and low-grade HCC (P<0.05 for all comparisons) compared to the controls. The ADC and volume ratios exhibited significant inverse correlations (P<0.001, R2=0.679). ADMSC-derived exosomes promoted NKT-cell antitumor responses in rats, thereby facilitating HCC suppression, early ADC increase, and low-grade tumor differentiation. ADC may be an early biomarker of treatment response.

Original languageEnglish
Article number853506
JournalStem Cells International
Volume2015
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 Sheung-Fat Ko et al.

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