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

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 nanoparti...

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Main Authors: Sheung-Fat Ko, Hon-Kan Yip, Yen-Yi Zhen, Chen-Chang Lee, Chia-Chang Lee, Chung-Cheng Huang, Shu-Hang Ng, Jui-Wei Lin
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/853506
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author Sheung-Fat Ko
Hon-Kan Yip
Yen-Yi Zhen
Chen-Chang Lee
Chia-Chang Lee
Chung-Cheng Huang
Shu-Hang Ng
Jui-Wei Lin
author_facet Sheung-Fat Ko
Hon-Kan Yip
Yen-Yi Zhen
Chen-Chang Lee
Chia-Chang Lee
Chung-Cheng Huang
Shu-Hang Ng
Jui-Wei Lin
author_sort Sheung-Fat Ko
collection DOAJ
description 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.
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institution Kabale University
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spelling doaj-art-727da5752c4f4cfa94a049e7930984cd2025-02-03T01:07:01ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/853506853506Adipose-Derived Mesenchymal Stem Cell Exosomes Suppress Hepatocellular Carcinoma Growth in a Rat Model: Apparent Diffusion Coefficient, Natural Killer T-Cell Responses, and Histopathological FeaturesSheung-Fat Ko0Hon-Kan Yip1Yen-Yi Zhen2Chen-Chang Lee3Chia-Chang Lee4Chung-Cheng Huang5Shu-Hang Ng6Jui-Wei Lin7Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDivision of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Medical Researches, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Medical Researches, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanWe 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.http://dx.doi.org/10.1155/2015/853506
spellingShingle Sheung-Fat Ko
Hon-Kan Yip
Yen-Yi Zhen
Chen-Chang Lee
Chia-Chang Lee
Chung-Cheng Huang
Shu-Hang Ng
Jui-Wei Lin
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
Stem Cells International
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://dx.doi.org/10.1155/2015/853506
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