Anti-tumorigenic effects of naive and TLR4-primed adipose-derived mesenchymal stem cells on pancreatic ductal adenocarcinoma cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background One of the main reasons for the unsuccessful treatment of pancreatic cancer is the intense desmoplastic pancreatic microenvironment. In the literature, the effects of mesenchymal stem cells (MSCs) and their inflammatory phenotypes on cancer cells have been a subject of controversy. Therefore, it is crucial to elucidate the underlying mechanisms of this interaction, especially in the context of pancreatic cancer. We aimed to investigate the effects of naive, TLR4-activated, and TLR4-inhibited phenotypes of adipose-derived MSCs (ADMSC) on pancreatic ductal cell line (Panc-1). Methods and materials Adipose-derived MSCs were induced into a proinflammatory phenotype using a 0.5 μg/mL dose of TLR4 agonist, while an anti-inflammatory phenotype was generated in ADMSCs using a 25 μg/mL dose of TLR4 antagonist. We observed that the proliferation of Panc-1 cells was inhibited when naive ADMSCs:Panc-1(10:1) and proinflammatory ADMSCs:Panc-1(10:1) were directly cocultured. Results In indirect coculture, both naive and proinflammatory ADMSCs exhibited a significant 10-fold increase in their inhibitory effect on the proliferation and colony forming capacity of Panc-1 cells, with the added benefit of inducing apoptosis. In our study, both naive and proinflammatory ADMSCs were found to regulate the expression of genes associated with metastasis (MMP2, KDR, MMP9, TIMP1, IGF2R, and COL

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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