Therapeutic potential of iPSC-exosomes and miR-7 in Targeting Glioblastoma

• Exosomes derived from induced pluripotent stem cells (iPSCs) exhibit anti-tumor effects in glioblastoma cell lines. • miR-7 enhances the therapeutic potential of iPSC-exosomes in GBM models. • Combination therapy (iPSC-exos + miR-7) shows additive/synergistic inhibition of tumor traits. • Treatment suppresses oncogenic markers (EGFR, MMP2, Raf1, CCND1). • Study provides a foundation for cell-free, miRNA-based glioblastoma therapy development. Exosomes play a vital role in intercellular communication, significantly influencing cell behavior and fate. Their influence is particularly evident in diseases like glioblastoma, one of the most challenging cancers to treat. Due to glioblastoma’s high resistance to conventional therapies, novel treatment strategies are urgently needed. Exosomes, being nano-sized vesicles capable of crossing the blood–brain barrier, can deliver bioactive molecules, including nucleic acids, proteins, and metabolites, to suppress tumor-promoting activities in cancer cells. Induced pluripotent stem cells (iPSCs), known for their unlimited proliferation potential and lack of ethical concerns compared to embryonic sources, present a valuable source of exosomes for therapeutic purposes. Although embryonic stem cell-derived exosomes have shown anti-tumor effects against glioblastoma, the therapeutic potential of iPSC-derived exosomes remains largely unexplored. In this study, we demonstrate that exosomes derived from iPSCs exert anti-tumorigenic effects on glioblastoma cells. We also focused on microRNAs (miRNAs), key regulators of cellular proliferation and apoptosis, which are considered promising therapeutic targets in glioblastoma. Specifically, we observed that microRNA-7 (miR-7) significantly inhibits glioblastoma cell proliferation, migration, and invasion. Our findings show that treatment with a miR-7-5p mimic reduces glioblastoma cell proliferation, and its combination with iPSC-derived exosomes leads to either additive or synergistic anti-cancer effects. These results highlight iPSC-derived exosomes and miR-7 as promising therapeutic candidates for glioblastoma and potentially other malignancies.