Placenta-derived extracellular vesicles support maternal adaptations during pregnancy by inducing immune tolerance, promoting angiogenesis, and regulating cellular function through autocrine and paracrine signaling. Recent research highlights the transformative potential of placenta-derived extracellular vesicles in modulating cell phenotypes for both cancer therapy and tissue repair. By facilitating the horizontal transfer of bioactive molecules, including proteins, and RNAs, they are now recognized for their modulatory effects on recipient cells, influencing tumor invasion and metastasis, inflammation, as well as stem cell renewal and expansion.

This Research Topic will consolidate current advances in the therapeutic application of placental extracellular vesicles, emphasizing their dual role in oncology and regenerative medicine. Contributions will explore how these nanosized vesicles reprogram cancer cell behavior, influence proliferation, invasiveness, and resistance, while modulating immune responses within the tumor microenvironment. Simultaneously, this Topic will highlight extracellular vesicles regenerative potential through intercellular signaling that promotes angiogenesis, stem cell recruitment, and anti-inflammatory effects. In addition, the Topic aims to bridge mechanistic insights with translational strategies, offering a comprehensive overview

This special issue aims to showcase and critically examine recent advances in the therapeutic application of extracellular vesicles derived from placenta bridging basic science and translational strategies, and fostering interdisciplinary dialogue to accelerate their clinical application in cancer therapy and regenerative medicine. Contributions may span mechanistic insights, translational approaches, and clinical perspectives that highlight the versatility of placental extracellular vesicles as next-generation bioactive agents.

We welcome original research and review articles addressing the following themes:

• Mechanistic insights into how placental placenta-derived extracellular vesicles reprogram recipient cancer cell phenotype and reshape tumor microenvironment;

• Immunomodulatory effects of placental extracellular vesicles within the tumor microenvironment, including their role in immune evasion and immune activation;

• Immunomodulatory effects of placental extracellular vesicles in regenerative niches;

• Regenerative functions of placental extracellular vesicles (promoting angiogenesis, stem cell recruitment, and anti-inflammatory signaling);

• Advances in extracellular vesicles multi-omics profiling, cargo optimization and scalable isolation techniques to support clinical translation;

• Development of placental extracellular vesicles as targeted drug delivery systems with high specificity and low toxicity;

• Integration of placenta-derived extracellular vesicles into biomaterial-assisted delivery platforms that improve local retention and enable sustained release, thereby improving their therapeutic efficacy in cell-free strategies for tissue regeneration.

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Transformative potential of placenta-derived extracellular vesicles in modulating cell phenotypes for both cancer therapy and tissue repair