Distinct anticancer properties of exosomes from induced mesenchymal stem cells vs. bone marrow-derived stem cells in MCF7 and A549 models.

MCF7 和 A549 模型中诱导间充质干细胞与骨髓来源干细胞的外泌体具有不同的抗癌特性

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作者:Ababneh Nidaa A, Aldiqs Razan, Nashwan Sura, Ismail Mohammad A, Barham Raghda, Al Hadidi Sabal, Alrefae Aya, Alhallaq Farah K, Abu-Humaidan Anas Ha, Saleh Tareq, Awidi Abdalla
Mesenchymal stem cells (MSCs) have significant potential in regenerative medicine due to their multipotency, however, they face clinical challenges such as limited expansion and heterogeneity. Induced pluripotent stem cell-derived MSCs (iMSCs) are promising alternatives. The present study compared the effects of exosomes from bone marrow stromal MSCs (BMSCs) and iMSCs on A549 and MCF7 cancer cells to explore the unique properties of iMSCs. Proliferation assays revealed that both exosome types inhibited MCF7 and A549 cell proliferation at 24 h (P≤0.0001 for both) compared with the control, with BMSC-exosomes (Exos) exerting a more significant effect on MCF7 cells (P≤0.01). After 48 h, the significant effects of the BMSC-Exos were no longer observed on either cell line, whereas the iMSC-Exos continued to suppress A549 cell proliferation (P≤0.001 compared with the control; P≤0.01 compared with BMSC-Exos), indicating a longer-lasting effect. An investigation of senescence-associated β-galactosidase (SA-βGal) activity revealed no significant effect on senescence induction in MCF7 cells treated with either type of exosomes. By contrast, compared with the control treatment, the treatment of A549 cells with exosomes resulted in a significant increase in the number of senescent cells (P≤0.0001). While the apoptosis assay performed by flow cytometry revealed no significant effect on apoptosis, this increase in senescence aligned with the decreased proliferation observed in A549 cells, indicating that the antitumor effect of the exosomes on A549 cells was mediated partially through the induction of senescence. Wound healing assays revealed that BMSC-Exos significantly increased the migration of MCF7 cells at 20 h (P≤0.01). However, this effect was reversed at 47 h (P≤0.05), indicating a time-dependent effect of BMSC-Exos. In A549 cells, no significant difference in migration was observed after treatment with either exosome preparation. These findings highlight the distinct effects of iMSC- and BMSC-derived exosomes on cancer cells, emphasizing the need for further investigations into their therapeutic potential and underlying mechanisms.

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