Abstract
Human mesenchymal stromal cells (MSCs) have been widely investigated both for regenerative medicine and their antinflammatory/immunomodulatory capacity. However, their ability to home pathological tissues suggested the development of strategies for using MSCs as carrier to deliver drug into tumor microenvironment. MSCs obtained from different tissues can be loaded in vitro with anti-cancer drugs by a simple procedures. In this report, we studied MSCs isolated and expanded from gingival papilla (GinPa-MSCs), by testing their ability to uptake and release three important anti-neoplastic drugs: Paclitaxel (PTX), Doxorubicin (DXR) and Gemcitabine (GCB). The efficacy of drugs releasing GinPa-MSCs was studied on a pancreatic cancer cell line and confirmed in vitro against a line of tongue squamous cell carcinoma (SCC154). Our results demonstrated that GinPa-MSCs efficiently incorporate the drugs and then released them in active form and in sufficient amount to produce a dramatic inhibition of squamous cell carcinoma growth in vitro. If compared with other MSCs sources, the collection of GinPa-MSCs is poorly invasive and cells can be easily expanded and efficiently loaded with anti cancer drugs. In particular, gemcitabine loaded GinPa-MSCs provide a good “cell-mediated drug delivery system” for a future potential application in the context of the oral oncology.
Highlights
Towards inflammatory microenvironments and to reach tumour sites after their systemic administration
We put particular attention in verifying the in vitro anticancer activity of the drug-releasing GinPa-mesenchymal stromal cells (MSCs) against a tongue squamous cell carcinoma cell line (SCC154)
The in vitro activity of PTX, GCB and DXR evaluated on the two human carcinoma cell lines CFPAC-1 and SCC154 showed a similar dose-response kinetics (Fig. 1)
Summary
Towards inflammatory microenvironments and to reach tumour sites after their systemic administration. To develop new therapeutic approaches based on anti-cancer molecules MSC-mediated delivery, engineered MSCs7, 8 were used; in addition, the ability of MSCs to uptake and release drugs without any genetic manipulation[9,10,11] was exploited. Among the different sources of MSCs, studies have been conducted using bone marrow MSCs that have some limitations concerning the discomfort caused in the donors. For this purpose, the ability of different sources of MSCs to uptake/release drugs[9,10,11,12,13] has been evaluated. We put particular attention in verifying the in vitro anticancer activity of the drug-releasing GinPa-MSCs against a tongue squamous cell carcinoma cell line (SCC154)
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