Cell Therapy Center, The University of Jordan, Amman, Jordan.
Department of Pharmaceutical science, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
Pathol Oncol Res. 2021 Apr 8;27:584710. doi: 10.3389/pore.2021.584710. eCollection 2021.
The therapeutic potential of mesenchymal stem cells (MSCs) for various malignancies is currently under investigation due to their unique properties. However, many discrepancies regarding their anti-tumoral or pro-tumoral properties have raised uncertainty about their application for anti-cancer therapies. To investigate, if the anti-tumoral or pro-tumoral properties are subjective to the type of MSCs under different experimental conditions we set out these experiments. Three treatments namely cell lysates (CL), serum-free conditioned media and FBS conditioned media (FBSCM) from each of Wharton's Jelly MSCs and Bone Marrow-MSCs were applied to evaluate the anti-tumoral or pro-tumoral effect on the glioma cells (U87MG). The functional analysis included; Morphological evaluation, proliferation and migration potential, cell cycle analysis, and apoptosis for glioma cells. The fibroblast cell line was added to investigate the stimulatory or inhibitory effect of treatments on the proliferation of the normal cell. We found that cell lysates induced a generalized inhibitory effect on the proliferation of the glioma cells and the fibroblasts from both types of MSCs. Similarly, both types of conditioned media from two types of MSCs exerted the same inhibitory effect on the proliferation of the glioma cells. However, the effect of two types of conditioned media on the proliferation of fibroblasts was stimulatory from BM-MSCs and variable from WJ-MSCs. Moreover, all three treatments exerted a likewise inhibitory effect on the migration potential of the glioma cells. Furthermore, we found that the cell cycle was arrested significantly at the G1 phase after treating cells with conditioned media which may have led to inhibit the proliferative and migratory abilities of the glioma cells (U87MG). We conclude that cell extracts of MSCs in the form of secretome can induce specific anti-tumoral properties in serum-free conditions for the glioma cells particularly the WJ-MSCs and the effect is mediated by the cell cycle arrest at the G1 phase.
间充质干细胞 (MSCs) 由于其独特的特性,目前正在被研究用于各种恶性肿瘤的治疗潜力。然而,关于它们的抗肿瘤或促肿瘤特性的许多差异,使得它们在癌症治疗中的应用存在不确定性。为了研究在不同实验条件下,MSC 的抗肿瘤或促肿瘤特性是否取决于 MSC 的类型,我们进行了这些实验。我们分别从牙髓间充质干细胞和骨髓间充质干细胞中提取了三种处理方法,即细胞裂解物(CL)、无血清条件培养基和 FBS 条件培养基(FBSCM),以评估它们对神经胶质瘤细胞(U87MG)的抗肿瘤或促肿瘤作用。功能分析包括:对神经胶质瘤细胞的形态学评价、增殖和迁移能力、细胞周期分析和凋亡。添加成纤维细胞系来研究处理方法对正常细胞增殖的刺激或抑制作用。我们发现,细胞裂解物对两种类型的 MSC 来源的神经胶质瘤细胞和成纤维细胞的增殖均产生了普遍的抑制作用。同样,两种类型的 MSC 的两种类型的条件培养基对神经胶质瘤细胞的增殖均产生了相同的抑制作用。然而,两种类型的条件培养基对成纤维细胞增殖的影响在 BM-MSCs 中是刺激的,而在 WJ-MSCs 中则是可变的。此外,三种处理方法均对神经胶质瘤细胞的迁移能力产生了类似的抑制作用。此外,我们发现用条件培养基处理细胞后,细胞周期明显被阻滞在 G1 期,这可能导致抑制神经胶质瘤细胞(U87MG)的增殖和迁移能力。我们得出结论,MSC 的细胞提取物以分泌组的形式,可以在无血清条件下诱导神经胶质瘤细胞的特异性抗肿瘤特性,特别是 WJ-MSCs,其作用是通过细胞周期阻滞在 G1 期来介导的。