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以及骨髓间充质干细胞在肝癌治疗中的治疗评估。

and therapeutic evaluation of bone marrow-derived mesenchymal stem cells in liver cancer treatment.

作者信息

Johor Abdulrahman, Mahadiuzzaman A S M, Alqusayer Abdulaziz Abdullah, Alkarim Saleh Abdulaziz, Opo F A Dain Md

机构信息

Department of Biological Science, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

Embryonic Stem Cell Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Front Cell Dev Biol. 2025 May 8;13:1521809. doi: 10.3389/fcell.2025.1521809. eCollection 2025.

Abstract

Hepatocellular carcinoma is the seventh most common kind of cancer worldwide and the second largest cause of cancer-related deaths in males, behind lung cancer. Globally, 866,000 people were diagnosed with hepatocellular carcinoma (HCC) in 2022, and nearly 42,240 new cases will be identified in 2025 in the United States. Using stem cells obtained from bone marrow can effectively reduce the number of malignant tumor cells through the induction of an epigenetic impact. We obtained bone marrow-derived mesenchymal stem cells (BM-MSCs) from mice and collected the conditioned medium (CM) from cultured cells with 90% confluency. The effect of the CM was identified using both 2D and 3D sphere cultures of wild-type human liver cancer cell line (HepG2), considering variations in sphere size and percentage. A cell death study was conducted using the cell cytotoxicity (MTT) kit, while the quantity of stem cells was determined by immunohistochemistry and gene expression analysis. The effectiveness of our therapy was demonstrated by an assessment of BM-MSCs through intravenous injection and the currently available anticancer drug cisplatin. , the combination treatment resulted in a synergetic effect, leading to 74% cell death in both adherent and spherical cultures when treated with 25 µM of cisplatin and 90%CM. , the histological study indicated a decrease in tumor size and number following treatment with cisplatin and BM-MSCs. The study lasted 18 weeks and revealed that the body weight of mice improved across all treatment groups, with the combination group exhibiting the most significant improvement. Both and studies showed the synergetic effect of cisplatin and isolated conditioned medium. Our study aimed to identify more efficient therapeutic approaches utilizing stem cells and existing marketed medications to minimize adverse effects with better efficacy.

摘要

肝细胞癌是全球第七大常见癌症,也是男性癌症相关死亡的第二大原因,仅次于肺癌。2022年,全球有86.6万人被诊断为肝细胞癌(HCC),2025年美国将新增近42240例病例。利用从骨髓中获取的干细胞,通过诱导表观遗传影响,可以有效减少恶性肿瘤细胞的数量。我们从小鼠身上获取骨髓间充质干细胞(BM-MSCs),并从90%汇合度的培养细胞中收集条件培养基(CM)。考虑到球体大小和百分比的变化,使用野生型人肝癌细胞系(HepG2)的二维和三维球体培养来确定CM的效果。使用细胞毒性(MTT)试剂盒进行细胞死亡研究,同时通过免疫组织化学和基因表达分析来确定干细胞的数量。通过静脉注射BM-MSCs和目前可用的抗癌药物顺铂对BM-MSCs进行评估,证明了我们治疗方法的有效性。联合治疗产生了协同效应,当用25µM顺铂和90%CM处理时,贴壁培养和球体培养中的细胞死亡率均达到74%。组织学研究表明,顺铂和BM-MSCs治疗后肿瘤大小和数量减少。该研究持续了18周,结果显示所有治疗组小鼠的体重均有所改善,联合治疗组改善最为显著。研究和研究均显示了顺铂和分离的条件培养基的协同效应。我们的研究旨在确定更有效的治疗方法,利用干细胞和现有的上市药物,以在提高疗效的同时尽量减少不良反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/190b/12095274/770ba4205272/fcell-13-1521809-g001.jpg

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