In vitro inhibition of oral squamous cell carcinoma by drug loaded gingival mesenchymal stromal cells (GinPa-MSCs)

OBJECTIVE: Mesenchymal stromal cells (MSCs) are widely studied for both their regenerative potential and their anti-inflammatory/immunomodulatory capacity. Furthermore, the capacity of MSCs to uptake and release drugs without any genetic manipulation was recently exploited, and their ability to home pathological tissues suggested a possible use for drug delivery into the tumor microenvironment. Here we explore the effect of drugs-loaded MSCs against squamous cell carcinoma (SCC), a malignant neoplasm which constitute the 95% of the head and neck carcinoma primarily originated from lip-oral cavity, pharynx and larynx. MATERIALS AND METHODS: MSCs isolated and expanded from gingival papilla (GinPa-MSCs) were loaded with anticancer drugs such as Paclitaxel (PTX), Doxorubicin (DXR) and Gemcitabine (GCB) according to a previous standardized procedure. The capacity of drugs loaded GinPa-MSCs to release the drugs was evaluated in vitro against a tongue squamous cell carcinoma cell line (SCC154) by using a MTT assay. RESULTS: GinPa-MSCs are less sensitive to the tested drugs than cancer cells and efficiently incorporate and release a sufficient amount of active drugs causing a dramatic inhibition of squamous cell carcinoma cell growth in vitro. The evaluation of the activity of drug released by cells in the conditioned medium, confirmed that after 24 hours, the cells released 62.6% of PTX, 91.8% of GCB and 100% of DXR. The conditioned medium collected from untreated GinPa-MSCs did not affect SCC cell proliferation. Furthermore, the presence in the condition medium of some cytokines such as hIL-6, hIL-8, hVEGF, hGROa, hSCGF-b, at concentration ranging from 13 to 24 ng/ml, does not seem to have any inhibiting or enhancing effect on SCC154 proliferation. CONCLUSION: The collection of autologous GinPa-MSCs is an easy procedure that can be performed without any discomfort for the patient and it can be easily expanded to obtain large number of mesenchymal stromal cells also for banking. The use gingival MSCs as a carrier for delivery anti-tumor molecules is of great interest also for the anatomic homology of the source with the type of cancer originating into the oral cavity. This means that drug loaded GinPa-MSCs with anticancer agents, GCB or PTX in particular, could be suitable for possible in situ advanced cell therapies (e.g.,in pre-cancerous stage, as adjuvant therapy to reduce the toxicity related to systemic treatment, to prevent cancer recurrences after surgical treatment, to reduce the radiation treatment effects, etc.