Extracellular Vesicles Derived from Human Embryonic Stem CellsReduce The Stemness Properties of Cancer Cell Lines
نویسندگان
1 Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran
2 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
3 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
4 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
5 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
6 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
7 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
8 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
doi
10.22074/cellj.2025.2049975.1768چکیده
Objective: Aggressive cancer cells exhibit many phenotypic and functional similarities to embryonic stem cells (ESCs),including characteristics such as self-renewal, differentiation flexibility, and specific gene expression signatures. Whilethe ESC microenvironment precisely regulates proliferation to balance self-renewal and differentiation, it remains unclearwhether tumor cells can respond to these regulatory signals to suppress their tumorigenic phenotype. Extracellularvesicles (EVs) released by human ESCs (hESCs) are known to exert paracrine effects, making them prime candidatesfor carrying these regulatory signals. The aim of this study was to determine if hESC-EVs suppress the tumorigenicphenotype of aggressive cancer cells by affecting their proliferative, invasive, and stem cell properties.Materials and Methods: In this experimental study, EVs were isolated from hESC-conditioned medium (hESC-CM)and thoroughly characterized. Aggressive breast and melanoma cancer cell lines were treated with the isolated hESCderivedEVs (hESC-EVs). The resulting effects on cell growth (proliferation), invasion, stem cell properties (stemness),and overall tumorigenesis were evaluated in vitro and in vivo. Expression levels of key pluripotency markers were alsoassessed in the treated cancer cells.Results: The treatment of the aggressive cancer cell lines with hESC-EVs resulted in a significant reduction in proliferation,invasion, stemness, and tumorigenesis across both in vitro and in vivo models. Mechanistically, exposure to hESC-EVs ledto the clear downregulation of pluripotency markers within the recipient cancer cells.Conclusion: These findings suggest that hESC-EVs transmit powerful regulatory signals capable of inducing the lossof stem cell characteristics in aggressive cancer cells. This mechanism offers a potential pathway for reprogramminghighly malignant tumor cells toward a more differentiated and less aggressive phenotype, suggesting a novel strategyfor anti-cancer therapy.
