Effect of bone marrow–derived mesenchymal stromal cells on hepatoma

IF 3.2 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Cytotherapy Pub Date : 2014-09-01 DOI:10.1016/j.jcyt.2014.05.006
Somia H. Abd-Allah , Sally M. Shalaby , Amal S. El-Shal , Eman Abd Elkader , Samia Hussein , Emad Emam , Nehad F. Mazen , Mohammed El Kateb , Mha Atfy
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引用次数: 23

Abstract

Background aims

The aim of the study was to evaluate the effect of mesenchymal stromal cells (MSCs) on tumor cell growth in vitro and in vivo and to elucidate the apoptotic and anti-proliferative mechanisms of MSCs on a hepatocellular carcinoma (HCC) murine model.

Methods

The growth-inhibitory effect of MSCs on the Hepa 1–6 cell line was tested by means of methyl thiazolyl diphenyl-tetrazolium assay. Eighty female mice were randomized into four groups: group 1 consisted of 20 mice that received MSCs only by intrahepatic injection; group 2 consisted of 20 HCC mice induced by inoculation of Hepa 1–6 cells into livers without MSC treatment; group 3 consisted of 20 mice that received MSCs after induction of liver cancer; group 4 consisted of 20 mice that received MSCs after induction of liver cancer on top of induced biliary cirrhosis.

Results

MSCs exhibited a growth-inhibitory effect on Hepa 1–6 murine cell line in vitro. Concerning in vivo study, decreases of serum alanine transaminase, aspartate transaminase and albumin levels after MSC transplantation in groups 2 and 3 were found. Gene expression of α-fetoprotein was significantly downregulated after MSC injection in the HCC groups. We found that gene expression of caspase 3, P21 and P53 was significantly upregulated, whereas gene expression of Bcl-2 and survivin was downregulated in the HCC groups after MSC injection. Liver specimens of the HCC groups confirmed the presence of dysplasia. The histopathological picture was improved after administration of MSCs to groups 2 and 3.

Conclusions

MSCs upregulated genes that help apoptosis and downregulated genes that reduce apoptosis. Therefore, MSCs could inhibit cell division of HCC and potentiate their death.

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骨髓间充质间质细胞对肝癌的作用
背景目的本研究旨在探讨间充质基质细胞(MSCs)在体外和体内对肿瘤细胞生长的影响,并阐明其在小鼠肝细胞癌(HCC)模型中的凋亡和抗增殖机制。方法采用甲基噻唑二苯四氮唑法检测间充质干细胞对Hepa 1-6细胞株的生长抑制作用。80只雌性小鼠随机分为四组:第一组20只小鼠仅肝内注射MSCs;2组20只肝癌小鼠,接种Hepa 1-6细胞诱导肝细胞癌,不经MSC处理;第三组为肝癌诱导后接受MSCs的小鼠20只;第4组为20只小鼠,在诱导性胆汁性肝硬化的基础上,在诱导肝癌后接受MSCs治疗。结果smscs对小鼠Hepa 1-6细胞系有抑制生长的作用。在体内研究中,2组和3组间充质干细胞移植后血清谷丙转氨酶、天冬氨酸转氨酶和白蛋白水平下降。肝细胞癌组注射MSC后α-胎蛋白基因表达明显下调。我们发现,注射MSC后,HCC组caspase 3、P21和P53基因表达显著上调,而Bcl-2和survivin基因表达下调。肝细胞癌组的肝脏标本证实存在不典型增生。2组和3组给予MSCs后,组织病理图像有所改善。结论smscs上调细胞凋亡相关基因,下调细胞凋亡相关基因。因此,MSCs可以抑制HCC细胞分裂,加速其死亡。
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来源期刊
Cytotherapy
Cytotherapy 医学-生物工程与应用微生物
CiteScore
6.30
自引率
4.40%
发文量
683
审稿时长
49 days
期刊介绍: The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.
期刊最新文献
Table of Contents Editorial Board Aims and Scope Subscription information Advanced therapies require soft skills: insights from a National Academies Working Group.
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