In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel

Abstract

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of GinPaMSCs did not affect the growth of cancer cell lines tested in vitro, whereas the secretome of GinPaMSCs primed with paclitaxel (GinPaMSCs/PTX) exerted a significant anticancer effect. GinPaMSCs were able to uptake and then release paclitaxel in amounts pharmacologically effective against cancer cells, as demonstrated in vitro by the direct activity of GinPaMSCs/PTX and their secretome against both human pancreatic carcinoma and squamous carcinoma cells. PTX was associated with extracellular vesicles (EVs) secreted by cells (EVs/PTX), suggesting that PTX is incorporated into exosomes during their biogenesis. The isolation of mesenchymal stromal cells (MSCs) from gingiva is less invasive than that from other tissues (such as bone marrow and fat), and GinPaMSCs provide an optimal substrate for drug-priming to obtain EVs/PTX having anticancer activity. This research may contribute to develop new strategies of cell-mediated drug delivery by EVs that are easy to store without losing function, and could have a superior safety profile in therapy.