Aldiqs Razan, Nashwan Sura, Ismail Mohammad A, Saleh Tareq, Barham Raghda, Zihlif Malik, Ababneh Nidaa A
Faculty of Biological Sciences, The University of Jordan, Amman, Jordan.
J Biosci. 2025;50.
Exosomes (Exos) derived from mesenchymal stem cells (MSCs) are known to influence cancer cell behavior; however, the clinical use of MSCs is limited due to the gradual loss of their differentiation potential with continuous passaging. Induced mesenchymal stem cells (iMSCs) have emerged as a promising alternative source, but the effects of Exos derived from iMSCs (iMSC-Exos) on cancer cells remain incompletely understood. This study aims to compare the effects of iMSC-Exos with ADMSC-Exos derived from adipose tissue-derived mesenchymal stem cells (ADMSCs) on the viability, invasion, and migration of breast (MCF7) and lung (A549) cancer cells. Conditioned media from iMSCs and ADMSCs were collected for isolation and characterization of Exos. MCF7 and A549 cell lines were treated with iMSC- and ADMSC-Exos, and Exos uptake, cell viability, migration, senescence, and expression of and genes were evaluated. iMSCand ADMSC-Exos were successfully internalized into cancer cells, with a higher efficiency of ADMSC-Exos uptake in MCF7 cells. Cell viability decreased and migration increased in both cancer cell lines upon treatment. expression was significantly reduced in MCF7 cells following ADMSC-Exos treatment and in A549 cells after iMSC-Exos treatment. In contrast, expression was significantly reduced in MCF7 cells treated with both iMSC- and ADMSC-Exos, while it significantly increased in A549 cells after ADMSC-Exos treatment. A549 lung cancer cells showed a higher level of senescence than MCF7 breast cancer cells, particularly when treated with iMSC-Exos. Minimal overall differences were observed in viability, apoptosis, and migration assays between iMSC- and ADMSC-Exos in MCF7 and A549 cells. However, significant differences were observed in the senescence and expression of and genes across cancer cell lines. These findings highlight the importance of further investigation into the distinct effects of iMSC- and ADMSC-Exos on cancer cell biology.
已知源自间充质干细胞（MSC）的外泌体（Exos）会影响癌细胞行为；然而，由于随着传代次数的增加，MSC的分化潜能会逐渐丧失，其临床应用受到限制。诱导间充质干细胞（iMSC）已成为一种有前景的替代来源，但源自iMSC的外泌体（iMSC-Exos）对癌细胞的影响仍不完全清楚。本研究旨在比较iMSC-Exos与源自脂肪组织间充质干细胞（ADMSC）的ADMSC-Exos对乳腺癌（MCF7）和肺癌（A549）细胞活力、侵袭和迁移的影响。收集iMSC和ADMSC的条件培养基用于外泌体的分离和表征。用iMSC-Exos和ADMSC-Exos处理MCF7和A549细胞系，并评估外泌体摄取、细胞活力、迁移、衰老以及相关基因的表达。iMSC-Exos和ADMSC-Exos成功内化到癌细胞中，在MCF7细胞中ADMSC-Exos的摄取效率更高。处理后，两种癌细胞系的细胞活力均降低，迁移增加。ADMSC-Exos处理后MCF7细胞中的相关基因表达显著降低，iMSC-Exos处理后A549细胞中的相关基因表达显著降低。相反，iMSC-Exos和ADMSC-Exos处理的MCF7细胞中的相关基因表达均显著降低，而ADMSC-Exos处理后A549细胞中的相关基因表达显著增加。A549肺癌细胞比MCF7乳腺癌细胞表现出更高水平的衰老，特别是在用iMSC-Exos处理时。在MCF7和A549细胞中，iMSC-Exos和ADMSC-Exos在活力、凋亡和迁移测定中的总体差异最小。然而，在不同癌细胞系中，衰老以及相关基因的表达存在显著差异。这些发现凸显了进一步研究iMSC-Exos和ADMSC-Exos对癌细胞生物学不同影响的重要性。
