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Human skin‐derived fibroblasts used as a ‘Trojan horse’ for drug delivery
Author(s) -
Coccè V.,
Vitale A.,
Colombo S.,
Bonomi A.,
Sisto F.,
Ciusani E.,
Alessandri G.,
Parati E.,
Brambilla P.,
Brambilla M.,
La Porta C. A.,
Pessina A.
Publication year - 2016
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12811
Subject(s) - paclitaxel , in vitro , drug , pharmacology , stromal cell , melanoma , mesenchymal stem cell , drug delivery , in vivo , apoptosis , cell growth , cancer research , biology , chemotherapy , chemistry , microbiology and biotechnology , biochemistry , genetics , organic chemistry
Summary Background Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the ‘Trojan Horse’ concept. Human mesenchymal stem cells ( hMSC s) have been shown to play the role of new ‘horses’ in delivering anti‐tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts ( hSDF s) represent an interesting alternative to hMSC s, being easy to isolate, they could be an ideal candidate for this kind of procedure. Aim To investigate whether hSDF s can take up and deliver paclitaxel ( PTX ) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro . Methods hSDFs were primed with high doses of PTX , and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDF s were studied both under both normal and hypoxic conditions. Results hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro . The hypoxic conditions did not induce changes in cell cycle pattern and the uptake–release mechanism with PTX was not affected. Conclusions hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis.