Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Institute of Cell Biology, Medical University of Innsbruck, Biocenter, Innsbruck, Austria.
Curr Gene Ther. 2021;21(1):81-88. doi: 10.2174/1566523220666201005111126.
Mesenchymal stem cells (MSCs) are considered an interesting tool in cell therapy due to their unique features such as self-renewal, multi-potency, and pluripotency. The multifunctional properties of these cells are being investigated in many studies. The current research examined the influence of MSCs on the Molt-4 cell line as acute lymphoblastic leukemia (ALL) cells.
MSCs were cultured, characterized, and co-cultured with Molt-4 cells in a trans-well system. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to western blotting for protein expression assessment. Telomerase activity as well as cell senescence, were investigated by PCR-ELISA TRAP assay and β-galactosidase activity measurement, respectively.
It was found that MSCs resulted in a significant increase in the pro-caspase-8 and cleaved-caspase 8 and 9 expression levels. Furthermore, protein expression levels of GSK-3α/β and ERK1/2 were significantly decreased. The results also showed that MSCs caused significant decreases and increases in telomerase and β-galactosidase enzyme activity of Molt-4 cells, respectively.
It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis and cell senescence via caspase-8, 9 cascade and GSK-3α/β and ERK1/2 signaling pathways.
间充质干细胞(MSCs)因其自我更新、多能性和多能性等独特特性,被认为是细胞治疗中的一种有趣工具。这些细胞的多功能特性正在许多研究中进行研究。目前的研究检查了 MSCs 对急性淋巴细胞白血病(ALL)细胞 Molt-4 细胞系的影响。
培养、表征 MSC,并在 Trans-well 系统中与 Molt-4 细胞共培养。然后,在第 7 天收集单独培养的 Molt-4 和与 MSC 共培养的 Molt-4(10:1),并进行 Western blot 以评估蛋白表达。通过 PCR-ELISA TRAP 测定和β-半乳糖苷酶活性测定分别研究端粒酶活性和细胞衰老。
发现 MSCs 导致前胱天蛋白酶-8 和裂解胱天蛋白酶 8 和 9 的表达水平显著增加。此外,GSK-3α/β 和 ERK1/2 的蛋白表达水平显著降低。结果还表明,MSCs 导致 Molt-4 细胞的端粒酶和β-半乳糖苷酶酶活性分别显著降低和增加。
结论是与 Molt-4 细胞共培养的 MSC 可能通过胱天蛋白酶-8、9 级联和 GSK-3α/β 和 ERK1/2 信号通路参与促进 Molt-4 细胞凋亡和细胞衰老。