Hajighasemlou Saieh, Pakzad Saeedreza, Ai Jafar, Muhammadnejad Samad, Mirmoghtadaei Milad, Hosseinzadeh Faezeh, Gharibzadeh Safoora, Kamali Amir, Ahmadi Akbar, Verdi Javad
Tissue Engineering and Applied Cell Sciences, Tehran University of Medical Science, Tehran, Iran. Email:
Asian Pac J Cancer Prev. 2018 Jun 25;19(6):1627-1631. doi: 10.22034/APJCP.2018.19.6.1627.
Background: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer and the third leading cause of cancer-related death. sorafenib is used as a standard therapy to treat HCC. mesenchymal stromal cells (MSCs) have also been used to suppress HCC. Here we investigate the development of a xenograft model of liver cancer to study the homing of hpMSC-GFP cells, tumor kinetics and molecular characterizations of HCC. Methods: To create xenograft models of HCC, HepG2 cell lines were inoculated into the flanks of 9 nude mice bilaterally. Animals were then divided into three groups: the first group received hpMSC-GFP systemically, the second received intra-tumoral hpMSC-GFP and the third received PBS. The first two groups were sacrificed after 72 hours of MSCs injection but the third group was followed up for forty days. One tumor from each animal was then transferred to formalin buffer for H&E staining and immunohistochemistry analysis (KI67 and CD34), and the other tumor was used for ex-vivo imaging. Blood samples were taken from all subjects before sacrificing them. Results: Histopathological fidelity of heterotopic HePG2 xenograft models to human HCC tumors was demonstrated. Biochemical evaluation suggested the health of the animal’s liver and kidneys. Ex-vivo imaging illustrated homing of more hpMSC-GFP cells in tumor tissues derived from the group receiving intra-tumoral hpMSC-GFP. Conclusion: A standard method was used to inoculate tumor cells and the intervention was shown to be safe to liver and kidneys. Local injection of MSCs can be used as cell therapy to fight neoplasms.
肝细胞癌（HCC）是第五大最常被诊断出的癌症，也是癌症相关死亡的第三大主要原因。索拉非尼被用作治疗HCC的标准疗法。间充质基质细胞（MSCs）也已被用于抑制HCC。在此，我们研究肝癌异种移植模型的建立，以研究人胎盘间充质干细胞-绿色荧光蛋白（hpMSC-GFP）细胞的归巢、肿瘤动力学以及HCC的分子特征。方法：为创建HCC异种移植模型，将HepG2细胞系双侧接种到9只裸鼠的胁腹。然后将动物分为三组：第一组全身接受hpMSC-GFP，第二组瘤内接受hpMSC-GFP，第三组接受磷酸盐缓冲液（PBS）。在注射MSCs 72小时后处死前两组，但对第三组进行40天的随访。然后将每只动物的一个肿瘤转移至福尔马林缓冲液中进行苏木精-伊红（H&E）染色和免疫组织化学分析（KI67和CD34），另一个肿瘤用于体外成像。在处死所有受试者之前采集血样。结果：证实了异位HepG2异种移植模型对人HCC肿瘤的组织病理学保真度。生化评估表明动物肝脏和肾脏健康。体外成像显示在接受瘤内hpMSC-GFP的组所衍生的肿瘤组织中有更多的hpMSC-GFP细胞归巢。结论：采用标准方法接种肿瘤细胞，且干预措施对肝脏和肾脏显示安全。局部注射MSCs可作为对抗肿瘤的细胞疗法。
