Aslam Nazneen, Abusharieh Elham, Abuarqoub Duaa, Ali Dema, Al-Hattab Dana, Wehaibi Suha, Al-Kurdi Ban, Jamali Fatima, Alshaer Walhan, Jafar Hanan, Awidi Abdalla S
Cell Therapy Center, The University of Jordan, Amman 11942, Jordan.
Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan.
Mol Ther Oncolytics. 2020 Nov 26;20:147-165. doi: 10.1016/j.omto.2020.11.005. eCollection 2021 Mar 26.
Cancer stem cells (CSCs) use their stemness properties to perpetuate their lineage and survive chemotherapy. Currently cell-based and cell-free therapies are under investigation to develop novel anti-cancer treatment modalities. We designed this study to investigate how cell extracts of mesenchymal stem cells affect the growth of glioma stem cells . Gliospheres were generated from the U87MG cell line and treated with conditioned media of Wharton's jelly and bone marrow mesenchymal stem cells. The effects were investigated at the functional and molecular levels. Our results showed that conditioned media from both types of mesenchymal stem cells changed the morphology of spheres and inhibited the proliferation, invasion, and self-renewal ability of glioma stem cells. At the molecular level, metabolism interruption at oxidative phosphorylation, cell cycle arrest, cell differentiation, and upregulation of the immune response were observed. Furthermore, this effect was mediated by the upregulation of the gene inhibiting the Wnt pathway mediated by growth factor activity and downregulation of the gene activated by growth factor and cytokine activity, inhibiting multiple pathways. We conclude that different types of mesenchymal stem cells possess antitumor properties and their paracrine factors, in combination with anti-immune modalities, can provide practical therapeutic targets for glioblastoma treatment.
癌症干细胞（CSCs）利用其干性特性维持自身谱系并在化疗中存活。目前，基于细胞和无细胞疗法正在研究中，以开发新的抗癌治疗方式。我们设计了这项研究，以调查间充质干细胞的细胞提取物如何影响胶质瘤干细胞的生长。从U87MG细胞系生成胶质瘤球，并使用沃顿胶和骨髓间充质干细胞的条件培养基进行处理。在功能和分子水平上研究其效果。我们的结果表明，两种间充质干细胞的条件培养基均改变了球状体的形态，并抑制了胶质瘤干细胞的增殖、侵袭和自我更新能力。在分子水平上，观察到氧化磷酸化的代谢中断、细胞周期停滞、细胞分化以及免疫反应上调。此外，这种效应是由生长因子活性介导的Wnt通路抑制基因的上调以及生长因子和细胞因子活性激活基因的下调介导的，从而抑制了多种通路。我们得出结论，不同类型的间充质干细胞具有抗肿瘤特性，其旁分泌因子与抗免疫方式相结合，可以为胶质母细胞瘤治疗提供切实可行的治疗靶点。
