Introduction/Background Mesenchymal stem cells (MSCs) play a dual role in tumorigenesis (pro- and anti-tumorigenic), and their anti-cancer activity is recently widely studied. This research endeavors to elucidate the impact of HATMSC2-MVs (microvesicles derived from human immortalized MSCs isolated from adipose tissue) on the biology of primary ovarian cancer (OvCa) cells.

Methodology Cancer cells were obtained from post-operative (post-op.) tissue and ascitic fluid from patients with primary OvCa tumors (N=16). The impact of HATMSC2-MVs on the biological behavior of OvCa cells was investigated in vitro for: proliferation (MTT assay), migration (scratch test), and cell survival assessed by flow cytometry (Annexin/PI tests) and confocal microscopy (Syto 9/PI staining).

Results Before the functional assessment, internalization of DiD-positive HATMSC2-MVs into OvCa cells was confirmed by confocal microscopy. At day 3 after internalization of HATMSC2-MVs into OvCa cells a notable reduction of proliferative activity has been observed in cells isolated from post-op. tumor (p<0.01) and ascitic fluid (p<0.001) (MTT assay). OvCa treated with HATMSC2-MVs decreased migratory activity of tumor cells. The median value of relative scratch closure assessed for OvCa cells isolated from post-op. tumor was 0.88 compared to untreated cells, while for cells from ascitic fluid, the median was at the control level 1.06. HATMSC2-MVs treatment decreases the percentage of alive cells from 76.25% for untreated control to 50.94% for OvCa treated cells, and induces apoptosis in OvCa. Immunofluorescence staining confirmed the anti-cancer activity of HATMSC2-MVs by confocal microscopy. For cells from post-op. tumor treated with HATMSC2-MVs, the median value of the relative live/dead ratio was 0.95, while for cells from ascitic fluid revealed 1.06 compared to untreated control.

Conclusion This study demonstrates the possibility to inhibit OvCa cells growth and apoptosis induction after exposure of OvCa cells on HATMSC2-MVs treatment. Application of HATMSC2-MVs can enhance anti-cancer effects and may serve as a biotherapy supporting standard procedures.

Disclosures The authors declare no conflict of interests.